Bio Lecture 12-22 Transcripts PDF

As we were looking at the components of the control and communication network or the Ccn. and specifically, we were focusing on the nervous system. And so we looked at the main cell types in the adult central nervous system. The 1st one we looked at was neurons. We said that neurons are critical for...

As we were looking at the components of the control and communication network or the Ccn. and specifically, we were focusing on the nervous system. And so we looked at the main cell types in the adult central nervous system. The 1st one we looked at was neurons. We said that neurons are critical for the flow of information within the nervous system. We looked at the anatomy of the neuron and the design that makes them so great for information flow. We looked at the receiving end of the neuron, but the dendrites and the cell body. And then we looked at how that signal is propagated along the axon of the neuron, where it then reaches the axon terminal. And that's where neurotransmitter gets released from. We also said that neurons are built to signal specific target cells with a specific neurotransmitter. So again, this idea of specificity. And so each neuron only releases one type of neurotransmitter. And we're going to look at some of these different neurotransmitters and their networks in today's lecture. We also looked at unmyelinated versus myelinated axons, and we saw that myelin sheath that was wrapped around the axon, and how that increases the conduction speed of an electrical impulse. We also looked at the different cell types for producing that myelin. And so in the central nervous system, we said, it's the oligodendrocytes in the peripheral nervous system. It's the Schwann cells. And then we looked at some other cell types in the central nervous system. Astrocytes specifically which we said, were even more abundant than the neurons. We said that astrocytes have many roles, different roles within the central nervous system, and we looked at some of these different roles, and that astrocytes are very important for communication. So forming that tripartite synapse with the neurons to help facilitate communication in the central nervous system. And then, finally, we looked at the blood brain barrier. So those tight junctions that form between the endothelial cells preventing things like bacteria or toxins from entering the brain, but still allowing the passage of certain essential compounds and some drugs as well. So today, we're continuing on with the nervous system. But we're specifically looking at different neurotransmitters and their networks within the adult human. So focusing on neurotransmitters and neurotransmitter networks and looking at how they're involved in things like our emergent properties, such as our personality. So a key component of the Ccn is that communication through this network is chemical based. And we've said this before. We have chemical messengers or mediators that are involved in the Ccn and neurotransmitters are an example of some of these mediators and even emergent properties that we have so things like our emotions, our personalities, these are chemical based. So neurotransmitters play a role in our emergent properties, such as our personality and our brains do have segregation in that. There are areas of the brain that are more responsible for certain functions than others. But they're still networked together to make it possible to create our emergent properties. And again, the neurotransmitter networks are involved in this. And we'll take a look at this today. And one of the earliest examples of this, that our brains are responsible for our personalities goes back to the 18 hundreds with a man by the name of Phineas Gage, and that's a picture of him on the right hand side of the slide there. And so I do want to put this into context of the time when this occurred back in the 18 hundreds, when this was back in an age when people would be accused of things like witchcraft if they behaved differently or acted differently or a little bit odd. And so this idea that our brain was responsible for our personality was actually really unheard of at this time. so sort of keep that in mind as we go through and talk about. You know this scenario back in the 18 hundreds. So if we look at the image on the left. Here we can see that something has likely happened to Phineas Gage, probably indicating that he had some sort of an accident, and in fact, he did. Phineas Gage got an iron bar through part of his skull. The bar entered just below the orbit of the eye shown here, and then it went out through the top of the frontal lobe on the left hand side of his skull. And so this red line here just illustrates how that iron bar went through his skull. and then on the right again. This is an image of him. He clearly suffered some eye damage as a result of this accident, and he's pictured here holding that very iron bar that went through his skull. And so Phineas Gage is referred to as one of the most famous patients in neuroscience. He suffered a traumatic brain injury, destroying much of his frontal lobe. So the iron bar went right through his frontal lobe. Miraculously he did survive this incident, but he was so changed in terms of his personality as a result of this incident, and his friends even described him as an entirely different person. And so this was some of the 1st evidence that we have demonstrating that different areas of the brain are responsible for creating our emergent properties like our personality. And so, because there was one part of his brain that was destroyed, he became a very different person with a very different personality. And so this is taken here from an article written in the Journal of Neurology. I won't read the entire excerpt here. You can read it if you're interested. But this is the story of the Phineas Gage accident. And so I've highlighted the key parts on the slide down here. So most of the left frontal lobe was destroyed, and despite this horrific and traumatic brain injury, he could still speak, walk, and he had normal awareness. however, despite doing exemplary work in his job before the accident. This accident was actually caused on the job by an explosion. After the accident, Phineas's employer would not allow him to return to his position at work, he had become very changed in terms of his personality. So this article describes that he had become fitful, irreverent, very profane. He was impatient, and his mood would fluctuate massively. He was unable to proceed with any plans. He was very indecisive, and so clearly he couldn't continue to perform the job that he was doing before his accident. and according to his friends again, he was no longer gauge. He was very different person in terms of his personality. and so, about 7 years after his death, Phineas Gage's body was studied to try and understand how this traumatic brain injury was linked with the changes in personality that had overcome him as a result of this accident. And then, in 1994 researchers utilized neuroimaging techniques to reconstruct Gage's skull to determine the exact placement of his injury, and so their findings indicated that he had suffered injury and damage to both the left and right prefrontal cortex, which we now know that this would result in problems with rational decision making the processing of emotions. And so these were the types of personality, traits or emergent properties that his friends and his employer had described another study, conducted in 2,004, using computer assisted reconstruction to analyze the extent of the injury, found that the effects were exclusively attributed to the left frontal lobe. And then in 2012, there was new research that estimated that that iron bar destroyed about 11% of the white matter in Gage's frontal lobe and about 4% of his cerebral cortex. So the details of this specific details are not important. This is just trying to emphasize to you that this has been a very well studied area of neuroscience represents some of the very early evidence that traumatic brain injuries can result in changes in behavior and personality. And so this story of Phineas Gage has had a tremendous influence on the science of neurology and the specific changes that were observed in his behavior and pointed to emerging theories about the localization of brain function, or the idea that certain functions are associated with certain areas of the brain. And so nowadays we know this. But back in the 18 hundreds, this wasn't really known at the time. And so we know now, as it shows on the in the text, on the bottom, that the brain is segregated, yet networked in a way to make it responsible for creating emergent properties, such as personality, rational decision making and the processing of emotion. Okay, so before we look more closely at the neurotransmitter networks, one of the ways to look at the brain is to look at how it's anatomically organized with different imaging techniques. So this diagram here, you don't need to remember this diagram. You don't need to know how it's labeled. This is more of a functional aspect that we're trying to get across with this slide. So how to track functional changes, using imaging techniques. So looking at specific areas of the brain, and how these areas are networked together. And so the figure depicted on the right hand side, showing here there are 4 heads or brains, and here it goes from hearing words to seeing words, speaking words, and reading words, and if you look more closely at those diagrams. There are different areas of the brain that are lit up in terms of the activity that's being performed. And so we can see that not only are there somewhat different areas of the brain that are involved as the activity changes, but this also spans a large area of the brain. So it's not just localized to one area for each specific activity. And so this is the idea that different areas of the brain are networked together when we perform different activities. And so we know this because of different modern imaging techniques that trace activity in the brain to see which areas are affected when we perform certain activities. So there are 2 imaging techniques listed here that I want you to know, and they are positron emission, tomography or pet scanning and functional magnetic resonance, imaging or functional MRI. And so these are 2 modern day imaging techniques that we can use to look at specific regions of the brain and to identify which brain regions are active when we're performing certain functions. So the 1st is pet scanning. So this is a nuclear imaging test that uses a form of radioactive sugar or glucose. So a glucose tracer and this would be taken into the body. It's radioactive, but at a very low level. So this is not a dangerous procedure. And then we would track that radioactive, glucose tracer in the brain to see which areas of the brain are metabolically active. And so those would be the areas of the brain that are using more glucose as energy. And so we would simply trace that to see where it goes and then scan this, using this scanning technique, so trying to determine which areas of the brain may be involved when we're hearing or seeing, speaking, reading, etc. And so we can then use this sort of imaging technique and follow that radiolabeled glucose. And then you can see when cells are more metabolically active and being utilized more, this will identify the area of the brain that's more active during a certain activity. And so you may be wondering how something like a pet scan differs from regular MRI, or maybe a Ct scan or an X-ray. And so these are other imaging techniques that we've probably heard about before. Often those images are used to identify the location of something within the body, and so those are used for identifying location, whereas a pet scan goes beyond that. And so it identifies function because it uses this radioactive glucose tracer. And then it's taken up by those cells. And so the more that those cells are being used, the more glucose that they take up, the more metabolically active they are. And so that's the difference between a pet scan and some of these other imaging modalities that we may be more familiar with, that a pet scan isn't just identifying the location within the body. It's identifying function. So pet scanning can be used to identify certain diseases. For example, a rapidly growing cancer in the body, a rapidly growing tumor would be very happy to see that glucose come along, and it'll take up that glucose, and it'll light up in the pet scan as an area where there could be a rapidly growing mass of cells, such as something like a tumor. Now, this isn't definitive, that it's going to be a cancer or a cancerous mass. But it's an indication that you would have a rapidly growing area of cells within a certain area, and so often from those imaging techniques, the pet scan would be used together with something like an MRI or a Ct scan or an X-ray which are used to identify the location. And then pet scan. We can identify function. So how cells are working in the body. I've mentioned MRI, or magnetic resonance imaging as a way that we can determine location in the body. But the next type of imaging that we're going to talk about is a little bit different from that. So it's called functional MRI. And the word functional is really important here, because this type of imaging is more than just identifying a location in the body. It's now trying to determine which areas of the body. In this case the brain are more active during certain activities. And so again, getting at the idea of trying to use different techniques to look at the function within the brain. So functional. MRI measures brain activity by measuring changes associated with blood flow. So it relies on the fact that cerebral blood flow or blood flow to the brain and then neuronal activation within the brain that these 2 things are connected. So really, it's a measure of blood flow, and it measures something called deoxyhemoglobin and deoxyhemoglobin is paramagnetic. so deoxyhemoglobin is the form of hemoglobin in our red blood cells that doesn't have any oxygen associated with it and when hemoglobin is deoxygenated, it becomes slightly magnetic or paramagnetic. And so the presence of this, then, creates a slight magnetic field, and this is what the imaging technique is able to detect in the brain. So in a scan like this, a person's head would be placed in the scanner. And then, when that hemoglobin is deoxygenated, so without oxygen it becomes slightly, magnetically charged. And this is what, then shows up on the scanners. So functional, MRI can be a really cool, imaging technique to determine brain activity or brain function in response to performing a particular activity. And so that's really what I want you to know about these 2 imaging methods, one tracks a radioactive glucose, the other tracks hemoglobin or blood flow, and they can be used to trace areas of the brain or identify areas of the brain that are more metabolically active. And so that's where these images on the right hand side. That's where we would get images like this would be from either a pet scan or a functional MRI scan of the brain. and then the yellow text at the bottom. It says it has become quite apparent with these modern imaging techniques that areas of the brain, or that areas of activity or function within the brain don't always perfectly coincide with a defined anatomical zone. So, in fact, they can stretch over different regions of the brain. So not always trying to identify one specific anatomical site, it could be multiple sites or a network or an area of the brain that's affected when we perform certain functions. Okay? So the point of the rest of today's lecture is to discuss different neurotransmitter networks that we have within the biological system. So networks are then defined by neurons that use the same neurotransmitter. So we have 4 different neurotransmitter networks to talk about. We have the norepinephrine network, the serotonin network, the acetylcholine network and the dopamine network. And so when it says that the network is identified that by the neurons that use the same neurotransmitter, we would talk about dopaminergic neurons. So neurons that all release dopamine as the dopamine network for acetylcholine. We call them cholinergic neurons. And they all release acetylcholine. So you get the idea here. And so we can organize these clusters or networks based on the neurotransmitter that's being released. And those are the ones listed here on the slide in blue. And so if we look at this diagram here again. You don't need to know these specific brain regions. This is just meant to show you from a physiology textbook. The blue lines here and the arrows would be an example of one of those neurotransmitters that would be in a network following its route throughout the brain, dispersing itself throughout the brain. So just to get across this idea that neurons can be categorized by their common neurotransmitter that they use. And so just appreciating this idea of a neurotransmitter network. And so we're going to go through each of these different networks in a bit more detail. So the 1st one to talk about here is the Norepinephrine network norepinephrine. It's also called noradrenaline. It's a chemical messenger from the catecholamine family. And so it functions within the brain and throughout the body, and it can function both as a hormone or a neurotransmitter. And so today we'll talk about norepinephrine as a neurotransmitter. But it will come up again when we talk about the endocrine system and our hormones. And so it has dual functions. But for today we'll focus on norepinephrine as a neurotransmitter. So the general function of norepinephrine is to mobilize the brain and the body for action. So there's a list of things here on the slide that the Norepinephrine network modulates things like attention, arousal the sleep-wake cycle, learning, memory, pain, anxiety, mood. This is a big list, and, as you see, you'll see as we go through the other neurotransmitter networks, there's a lot of overlap in terms of the functions that these different neurotransmitter networks modulate. And so I'm not looking for you to memorize this list. But on a more general level is involved in mobilizing the brain and the body for action. So it's stimulatory. It's part of our fight or flight response. And so when there's a situation of stress or danger in the body, when the body needs to be mobilized and activated in some way, the Norepinephrine network is part of that. So as we go through each of these different neurotransmitter networks, maybe talk about either a disease or specific drugs that are associated with each neurotransmitter network. That's more the type of information that I would want you to know from this with regard to each neurotransmitter network rather than memorizing this list of things that are modulated by each neurotransmitter. So in terms of norepinephrine, some drugs that people might take things like psychostimulants are designed to induce a stimulatory effect and so they generally work by boosting norepinephrine levels in the body. So psychostimulants like methamphetamine, ritalin, caffeine. These are all drugs that fall under this category, and they promote the release of Norepinephrine, they stimulate the Norepinephrine network, and so some of us might have caffeine in the morning, as our morning coffee, maybe a Red Bull to promote alertness or awakeness. Caffeine when it binds to its receptor one of the things that it does is that it leads to the release of Norepinephrine. some drugs such as Ritalin, which is used to treat attention, deficit, hyperactivity, disorder, or Adhd in kids. It will also stimulate norepinephrine in the body another drug that's used for Adhd treatment is called Adderall, interestingly and sort of anecdotally. Ritalin and adderall may, in fact, be used by some students as what we call smart drugs or nootropics. And so we mentioned these when we talked about enhancement medicine, these nootropics. This would be the idea of taking drugs, not for a treatment or a medical need, but as a means to boost learning and to boost memory. And so they fall into this category when they're taken for enhancement purposes. So this would be the idea of nootropics or enhancement medicine. You're taking them for a specific purpose to improve learning or memory. As you study for an exam, for example. So the main thing to know about these drugs here is that they work by stimulating the norepinephrine network. So serotonin is another neurotransmitter. It has a popular image associated with it. Sunshine, as it contributes to feelings of well-being and pleasure or happiness, although its biological function is actually quite complex. So it's also involved in other things, such as cognition, reward, learning, and memory, numerous physiological processes. Serotonin is involved in as well as pain, and our sleep- wake cycle. Again, we know that serotonin is most well known for its effects on emotion, causing feelings of well-being and happiness. and most antidepressant drugs work through increasing serotonin levels. And so that's the main mechanism of action of most antidepressants is to boost the serotonin network and to boost serotonin function and specifically increase the release of serotonin. So again, it has multiple biological functions. But a key one is contributing to feelings of well- being and happiness. And again, that's the main mechanism that antidepressant medications work through. Interestingly, there's also associations with the functioning of the vascular system within the brain. So low serotonin levels have been associated with migraines or migraine headaches, and so many anti-migraine medications also work by boosting serotonin levels. And so you may take something because you're prone to having bad migraines. And so you may take an anti-migraine medication, and although it's not the intended purpose of that medication, you may also have this added effect that your serotonin levels are boosted, and that added effect of feelings of happiness or well-being when taking those medications for migraine headaches. So the next is the cholinergic network or the acetylcholine network. This is another neurotransmitter network in the body, and the main neurotransmitter is acetylcholine. It modulates again, things like arousal sleep wake cycles memory sensory information. So lots of overlap here again. It's not this list that I'm looking for you to memorize, because you can see again, there's a lot of overlap between the different neurotransmitters and some of the functions that they modulate. So that's not what I'm looking for here. But if we've highlighted something specific about one of the neuro transmitters and their networks a disease or a particular drug. That's more. What I would be interested in you, knowing from this. So Alzheimer's disease is probably the most classically defined disease that's characterized by the massive loss of cholinergic neurons. So a massive loss of the acetylcholine network. And again, we see a huge loss of cholinergic neurons with this disease as it progresses. And that's what's shown in these scans on the bottom left here. So these are likely obtained from one of those modern imaging techniques that we've talked about. So we can see here a scan of a normal brain, and then a brain with a mild, cognitive impairment, and then a brain with Alzheimer's disease. And while we don't know the specific details of each one of these scans, what it's showing you is that as we progress to more severe Alzheimer's disease, there's this massive loss of cholinergic neurons and very low acetylcholine, very low acetylcholine levels because it's these cholinergic neurons, those are the ones that produce the acetylcholine. So again, low acetylcholine levels. And again, the main characteristic of Alzheimer's disease is problems with memory. Now, there isn't much that we can do about the loss or the destruction of these Cholinergic neurons in Alzheimer's disease. The treatment here really becomes one of trying to treat the symptoms or manage the symptoms. So trying to boost acetylcholine levels is the main form of treatment that we have for Alzheimer's disease, and it's not a curative treatment, but it's just meant to help mitigate or alleviate some of the symptoms associated with Alzheimer's. so a drug would be given to try to boost the acetylcholine levels that are being produced by whichever Cholinergic neurons are remaining, so the disease is characterized by the loss of cholinergic neurons. But as long as we have some of those neurons still present, we can try to boost the acetylcholine that they're releasing or producing, and then try and maintain some level of health span in these individuals. And so if we think about some of the feedback mechanisms that we've spoken about with regard to neurotransmitters, one way to try and control the level of a neurotransmitter signal is to control the breakdown or degradation of that neurotransmitter within the synapse. So we talked about. When a neuron releases the neurotransmitter, we don't necessarily want that neurotransmitter to hang around there forever. So there's typically an enzyme that will degrade that neurotransmitter it'll quickly get rid of it, and it'll turn off that neurotransmitter signal or that response. And so the various drugs that are available in Canada to treat the symptoms of Alzheimer's disease. They play on this type of mechanism, and these are called cholinesterase inhibitors. So cholinesterase is the enzyme that will rapidly break down acetylcholine in the synapse. and so in a healthy individual, acetylcholine gets released from its cholinergic neuron into the synapse, and then that cholinesterase is going to break down or degrade it to decrease the acetylcholine levels and prevent that acetylcholine signal from continuing to persist. But in Alzheimer's disease we're trying to boost those acetylcholine levels. And so the drugs here the Cholinesterase inhibitors work by inhibiting the enzyme cholinesterase. And so they inhibit that enzyme that's going to degrade or break down acetylcholine, thereby trying to keep the acetylcholine levels up and elevated as much as possible. so not letting that acetylcholine be degraded as it would be in a normal, healthy individual. And so it's interesting that once we understand acetylcholine and how it works and what some of its functions are, how it's released or how it's degraded. We can then target that so that it's not degraded. We can keep those acetylcholine levels higher, and perhaps we can try and improve some of the health span in those individuals with Alzheimer's disease. Now, unfortunately, we can't go back and fix the destruction of those cholinergic neurons. So we have to work with trying to boost the low acetylcholine levels in the cholinergic neurons that remain. And so again, this treatment really becomes about mitigating or minimizing the symptoms of Alzheimer's disease. And so this is not a long term or a curative treatment. Eventually there will be 2 too much loss of these cholinergic neurons, and there's nothing else that can be done for Alzheimer's disease. So unfortunately, at this point, Alzheimer's is an incurable disease. Okay, the final network to talk about today is the dopamine network. So dopamine controls or modulates motor control and reward or pleasure centers in the body. So dopaminergic neurons release dopamine and dopamine is the neurotransmitter that's responsible for these actions on motor control or reward and pleasure. So we talked a little bit about dopamine before the midterm. We were talking about the teenage brain or emerging adult brain. And we said that at that stage of life there's an increased sensitivity of the brain to dopamine. And so in those years, those teenage years. With this increased sensitivity of dopamine there's a heightened response to reward or pleasure. This idea of a heightened social reward we talked about, and so we also talked about how this may lead to teenagers displaying more risky behaviors because of this increased sensitivity to dopamine in terms of the dopamine network. Parkinson's disease is the classic example of a disease where there's a loss of the dopamine network. And again, this is what's being shown here on this brain scan. So we have a normal brain scan, and then a scan from an individual with Parkinson's disease. and then on the bottom here shows a normal brain, and then a brain with early Stage Parkinson's, and then the progression to late stage Parkinson's disease. And so this shows the progressive loss of dopamine or dopaminergic neurons within the brain. The symptoms we see in patients with Parkinson's disease relates to the fact that the dopamine network is involved in motor control. So individuals affected by Parkinson's. There can be things like tremors of the hands or eye movements. Sometimes a patient with Parkinson's disease will shuffle their feet with the loss of dopamine. There's this problem with motor control, and so they may have a reduced sense of balance and motor control. And so they'll shuffle their feet as they walk. Because of this in terms of treatment for Parkinson's disease. It's a little bit like Alzheimer's in that. You're trying to treat or manage the symptoms by boosting those neurotransmitter levels. We're not able to do anything about the destruction of those dopaminergic neurons. But we can use dopamine agonists to try to boost the health span in individuals with Parkinson's disease. And so Parkinson's is not only an effect on motor control. Parkinson's patients can also suffer from certain behavioral things, such as a decrease in sexual desires. Again, because of that role of the dopamine network in our reward and pleasure centers. And so in terms of medication, too much medication or too much of this dopamine agonist. This can lead to other problems as well. And so there can be with this, with too much of a dopamine agonist, there can be an increase in sexual desires or hypersexuality, problems controlling impulses. So gambling may be an example. Something like food addiction can also result from this. And so again, these are problems that might occur if too much of that dopamine agonist is provided. And so this just shows the extent to which dopamine as a neurotransmitter is involved in controlling the functions within the biological system. So this slide here takes a closer look at the dopamine network, and the next slide will also look at some drugs that affect or interfere with the dopamine network. Dopamine, we said, is responsible for feeling good. It's the pleasure network in the body. So the dopamine signal gets processed in the prefrontal cortex of the brain. And so that's where the signal or action potential gets processed into that emergent property. It's where that good feeling of pleasure gets processed. And so if we think back to the beginning of lecture with Phineas Gage. And remember, he got that iron rod that went through the right prefrontal cortex. And then Phineas Gage had these changes in his personality that definitely would have affected the reward or pleasure center within his brain. The other thing about the dopamine network is that it's typically associated with addiction. And so this goes along with the function of dopamine. so dopamine can be increased by various drugs, such as cocaine. We'll talk about the mechanism of that in the next slide, but dopamine can also be increased by natural drugs if you will, or endorphins. The exercise induced euphoria as an example. So you've gone for a run, and then afterwards you feel really good. That's called runner's high, and that's through the release of dopamine and those natural endorphins that give you that good feeling or that feeling of euphoria. And so it's also thought that food can act through the dopamine network to give us that good feeling or feeling of pleasure within the body. And so what's shown in the diagram here is how we turn off the dopamine signal. And so I'll draw your attention to this red dopaminergic neuron here. So we have our cell body, our axon here. And so the action, potential or signal, gets transmitted along this axon where it reaches the axon terminal. And then that's where dopamine gets released into this synapse dopamine. If it acts on another neuron. So in this diagram, it's called the next neuron talked about it as the postsynaptic neuron. If dopamine acts on that next neuron, it's going to induce its response. And that's what's shown here. And that will lead to the effect of dopamine continuing to occur the propagation of that dopamine signal. But what's also shown in this diagram? Here is how we turn off the dopamine signal. So remember, we said, those neurotransmitters, they act very quickly, but then we also have to have a quick and efficient mechanism for turning that signal off. And so in this case, with the dopamine signal, this involves another neuron, and that's called the Gaba neuron. So Gaba stands for gamma amino, butyric acid, and it's an inhibitory neuron. So the Gaba neuron shown here in yellow again, we have our cell body and our axon. It's going to release Gaba into the synapse. And in this case, when Gaba is present, it's going to turn off the dopamine signal at the postsynaptic neuron here or the next neuron. So that's a way of turning off or shutting off the dopamine signal is through the inhibitory action of Gaba. And so Gaba doesn't work to prevent the release of dopamine. It's working to stop the action of the dopamine signal at the postsynaptic neuron or the next neuron. And interestingly, Gaba can be inhibited by different addictive drugs, such as heroin and morphine. And so, if you can imagine with these addictive drugs, they are inhibiting the action of Gaba. And so that means that the dopamine signal is going to be allowed to propagate. It's going to be allowed to continue. And this shutoff mechanism is inhibited. And so we'll talk about this a little bit more in the next slide. But importantly, the dopamine network is typically associated with drug addictions. Okay, so this slide here is a picture of how different drugs can work to control neurotransmitter levels. And in this case the neurotransmitter, again, is dopamine. And so this is how the base or this is the basis of how certain addictive drugs things like cocaine, amphetamines, heroin, morphine. This is the basis of how they work. So I do on this slide want you to pay attention to the different addictive drugs and their mechanisms. So how they act in some way or another, all of these drugs act to stimulate or enhance the dopamine network. So we'll 1st look at the graph on the left hand side or the picture on the left hand side. We have our dopaminergic neuron here shown in red. The axon terminal here is going to release the dopamine into this synapse, and then for dopamine to function. It's going to find its specific receptors on the postsynaptic neuron here, and those are shown in red as well. So dopamine, released into the synapse, finds its dopamine receptor, and then it induces its effect in the postsynaptic neuron. Now, the mechanism for turning this dopamine signal off, we have a reuptake mechanism in the presynaptic neuron. So that's what's shown here. Dopamine can actually be taken back up by the dopaminergic neuron that released it. So it's then taken back up or removed from the synapse. It's not going to continue to bind to the dopamine receptor on that postsynaptic neuron. And this is how we stop that effect or inhibit that effect. And then, as we've already mentioned, we also have the inhibitory neuron Gaba, and that's shown in yellow here. So Gaba is going to the Gaba neuron is going to release Gaba into the synapse here, and then Gaba will bind to its specific receptor shown in yellow on that postsynaptic neuron. And this because it's inhibitory, is going to turn off the action of dopamine. And so we have a couple of different ways here that we can turn down this dopamine signal. So then, how do these addictive drugs work? They can work through a few different mechanisms. And so that's what's shown here on the right hand side. The 1st one we have are amphetamines, and so amphetamines lead to the release of dopamine. That's a pretty straightforward one. Amphetamines will trigger the release of dopamine. They trigger the dopamine network. They cause these dopaminergic neurons to release more dopamine into the synapse. And that's what's shown here. And so that dopamine will then find its specific receptor in the postsynaptic neuron and induce its response of pleasure or reward. And so that's how amphetamines work the other addictive drugs that are shown here work by slightly different mechanisms, so cocaine shown on the bottom here is going to act through blocking this reuptake mechanism or the reuptake of dopamine. And so we have that reuptake mechanism as one as a way to shut off dopamine's effects. And so, if we block that reuptake dopamine can continue to have its effect, and so cocaine works by blocking this reuptake of dopamine by the dopaminergic neuron, thereby allowing the dopamine effect to continue to persist. Now cocaine works a little bit differently from heroin or morphine. So heroin and morphine work by blocking the release of Gaba. And that's what's shown here. And so in this case heroin and morphine will block Gaba release from the Gaba neuron. And so that release of Gaba will be inhibited or blocked. and so that Gaba will not get released into the synapse. It won't bind to these receptors. And so that feedback mechanism for turning off the dopamine signal is then lost. So you've blocked Gaba. You've blocked the inhibitory mechanism of Gaba, and then that dopamine signal will be allowed to continue. So it's definitely important to be aware of how these different types of drugs affect the dopamine network because these drugs have different mechanisms. It's known that if you stack these drugs or take these different types of drugs at the same time, what's known as stacking you can then have an even greater effect on the dopamine network, not to say that each of these highly addictive drugs they certainly have their their own potent effects on the body, but if you were to combine them in a cocktail, if you will, you will further stimulate the dopamine network because they work through these different mechanisms. And so if you target each of those mechanisms, you would get a greater or maximal effect on the dopamine system so important here that you do know the different mechanisms by which these drugs act. So one by promoting more release of dopamine, one by blocking the reuptake or clearance of dopamine, and then the other by blocking the negative feedback signal. That is Gaba. Okay, so just a practical example to finish things up today, putting some of these networks together. So the example here is alterations to the phenylalanine, hydroxylase pathway or pah in what's known as phenylketonuria, or pku. And so this pah pathway is shown on the left here, and it converts the amino acid called phenylalanine, to another amino acid called tyrosine and tyrosine, is a critical amino acid for the synthesis or formation of the neurotransmitter dopamine. And so Pku is a genetic condition that affects about one in 12,000 infants born in Canada. It's caused by a mutation in this pah gene that reduces the amount of enzyme that's responsible for converting this phenylalanine to tyrosine. So this, then, leads to reduced tyrosine levels and excess phenylalanine levels in the brain because we're not getting that conversion of phenylalanine to tyrosine. And so what happens is that this excess phenylalanine competes with other amino acids, specifically tyrosine and tryptophan. And that's what's shown here and so these. These amino acids, tyrosine and tryptophan, are essential in the synthesis of dopamine and serotonin. So with this this gene mutation that causes pku, there's a decrease in the neurotransmitters, dopamine and serotonin. And that's the result of these high phenylalanine levels. And so if we think about our discussion about these 2 neurotransmitter networks the dopamine network and the serotonin network. We said that serotonin is most known for its effects on our emotions, so feelings of well-being and happiness, our dopamine network modulates feelings of pleasure. It's also involved in motor control. And so, if we think about this, what might be some of the possible health implications of altering this pah pathway. So the pathway that leads to the conversion of amino acids that are important for the synthesis of these neurotransmitters. And so, indeed, the alterations of this pathway cause reductions in the dopamine and serotonin levels in individuals with pku. And so, therefore, this leads to behavioral symptoms in these individuals, including an increased risk for Adhd, or hyperactivity, as well as anxiety, impulsivity, mental illness, and low motivation, or low self-esteem as well. And so this is particularly evident in individuals with pku, especially when this condition is uncontrolled or unmanaged. And so then, if high phenylalanine levels are what drive this? The question on the bottom is, could a low phenylalanine diet mitigate these risks and the behavioral symptoms that are associated with it? And indeed it can. And so the main treatment for individuals with pku is that they follow a lifetime diet with very little intake of foods that contain phenylalanine. And so the slide here shows the top 10 foods that are highest in phenylalanine, and they're mainly animal proteins or animal products, pasta potatoes. So I don't expect you to know this list of high phenylalanine foods. This is just to show you that individuals with pku have to follow this diet that contains very little phenylalanine diet that's composed of a lot of fruits, vegetables. It's largely plant-based, and their necessary protein intake usually comes from some sort of protein substitute. So this is to then manage some of the symptoms associated with pku that are a result of low serotonin and low dopamine levels and the behavioral effects that this causes. So we'll leave things there for today, and we'll pick up next day talking about the endocrine system. Have a great day. So today, we're going to continue talking about the Ccn or the control and communication network and components of the Ccn. So we've already talked about the nervous system. And today we're going to be moving on to talking about the endocrine system. So talking about the role of different chemical messengers, and in particular, looking at some of the key hormones within the endocrine system. So, just as a recap from last day we continued our discussion on the nervous system, where we talked about how different areas of the brain are networked together to create our emergent properties, such as our personality. We looked at 2 different modern imaging techniques, and those were positron emission, tomography, or pet scanning. and then functional magnetic resonance, imaging or functional MRI. And so these imaging techniques are used to determine brain function and to identify which regions of the brain are active while we perform certain activities. We then looked at 4 different neurotransmitter networks. So the Norepinephrine network, we said, prepares the brain and the body for action. So part of our fight or flight response. And then we looked at drugs that that act to boost the norepinephrine network, and those are called psychostimulants. So caffeine or methamphetamines would be examples of those the serotonin network is most known for inducing feelings of well-being and happiness. and we said that most antidepressant medications work by increasing the serotonin levels in the body. The acetylcholine or cholinergic network uses the neurotransmitter acetylcholine, and the loss of this network is most associated with Alzheimer's disease and a main feature of Alzheimer's disease is, of course, issues with memory. And then the dopamine network was the last one that we looked at. It's most associated with drug addictions. So we looked at the mechanisms by which various addictive drugs, such as cocaine, amphetamines, heroin, morphine, the way that all of these drugs act, which is through inducing the dopamine network. And then we looked at the specific mechanisms. And it's important for you to understand these and sort of know the differences between how each of these drugs act on that dopamine network. And then, finally, we said, the loss of dopamine is associated with Parkinson's disease, and this leads to symptoms related to the loss of motor control. So we're going to carry on looking at the endocrine system today. And there are many aspects to looking at the endocrine system or endocrine physiology. In fact, you can take a whole course devoted to endocrine physiology. And so here, with one lecture, we're very much providing an overview of the endocrine system. So on this slide here we have some different examples of various hormones. Some of those are melatonin, which we talked about in our discussion of Circadian rhythms that is released as natural light declines towards the end of the day, and that this promotes sleep. We also have other examples, such as hydrocortisone. This is a cortisone, like steroid, that helps to reduce pain, swelling, itching that can be caused by inflammation or the body's immune response. We also have insulin and human growth hormone shown here and human growth. Hormone is key for growth and development. And we'll talk about that one today as well. We have the picture of 2 girls here. That's sort of depicting the change in height or the growth spurt that occurs during puberty. And so we know that growth hormone, and also the sex hormones play key roles. During this time of the lifespan we might also hear about the role of different hormones in enhancing athletic or sport performance. So the right hand side this shows Lance Armstrong. He's a famous cyclist. He was caught for using drugs illegally to enhance athletic performance, and in particular he was noted for doing this during the Tour de France. So in today's lecture, we'll look at the hormones involved in growth and development, and we'll also talk about some of the hormones or drugs that are used for enhancing sport or performance. And so the illegal use of these drugs to enhance athletic performance. So the role of hormones within the endocrine system is many fold. The role of hormones in growth and development is perhaps an obvious role of these chemical mediators. Hormones are involved in many different aspects within the biological system. In terms of physiology and metabolism. For example, they have important roles in maintaining homeostasis within the body. We know that the sex hormones play critical roles in reproductive processes within the body, and hormones also play many other roles within the communication or controlling communication network. And so they're involved in neurodevelopment or immunity or immune function. So playing an important role in our local support and defense system, or loosely our immune system. And so we'll talking. We'll start talking about the immune system in next class. So the similarity between the sex hormones is, in fact, quite surprising. And if this isn't something that you've ever looked at before or thought about before, this diagram here shows the different sex hormones. And so if we look at the top panel of that figure, we can see the 2 female sex hormones, progesterone and estrogen and estrogen is sort of a catch-all phrase for different forms of estrogen. So there are different forms of estrogen that the body produces with Estradiol being the most common one. You don't need to worry about that for this course. Here I'm just showing you pictures of progesterone and estrogen, so that you can appreciate the similarity in their chemical structures. The male sex hormone testosterone shown in the middle. Here we can see if we look across all 3 of those hormones. There's remarkable similarity in terms of the chemical structure of these hormones. And so the difference between testosterone and the 2 female sex hormones is largely a methyl group, so the addition of a ch. 3 group, or the addition of double bonds, or the placement of those bonds. And so I'm not concerned with you. Knowing these chemical structures, or even knowing the differences between them. I just want you to appreciate how similar they are in terms of their chemical structure, and even though they have these similarities in their structure. They have very different effects on the biological system. so, of course, they have their own specific receptors or different receptors that they bind to, and they trigger different signaling events within the cell when they bind to their specific receptor. And so the main point here is just trying to get you to appreciate the remarkable similarity between the chemical structures, but that we know within the biological system the binding of these hormones to their specific receptor induces different signaling events and therefore different effects or different functions within the biological system. Okay, so this is a diagram which has a lot of information on it. It's taken from a textbook. So this diagram shows the traditional view of where do hormones come from in the body? So what are the key? Endocrine glands in the body. What are some of the specific target organs that might produce hormones as a secondary function? This is essentially a classic understanding of where hormones come from, and it's arranged in sort of a hierarchy. Starting at the top of the diagram. Here we have the pituitary gland, the posterior lobe, and the anterior lobe which will be talking about in a few minutes. We also have our pineal gland, which we mentioned previously, is the gland that produces Melatonin. and then moving on down the diagram. We also have our parathyroid glands and our thyroid gland. And so then we get into sort of more the periphery. Here we have the stomach, which is a site for secreting various mediators and hormones, and we'll talk about the stomach more as an endocrine organ when we move into the gastrointestinal system. We then also have our adrenal glands and our pancreas, the sex organs in the body or the gonads, so either the testes or the ovaries which secrete our sex hormones. And so I don't want you to get too nervous about this diagram or feel like you need to memorize everything on this diagram as we go forward in today's lecture, I'll highlight key aspects of this that I would want you to know. So it's not a bad idea to be aware of these major endocrine glands in the body. We'll definitely be talking more about the pituitary gland, both the posterior lobe and the anterior lobe, and some of these other glands will definitely come up as well. So it's a good idea to have a general understanding, but you're certainly not responsible for everything that's listed here on this slide. So, as I mentioned, some of this will come up later in the course. So, for example, the idea that the stomach or the pancreas are major secretory organs within the body. So some of this we'll look through later in the course, and some of it. We'll look in more detail today. So again, this is more of a standard textbook view of the endocrine organs in the body. But at the bottom I've written in blue here, what is missing from this diagram? And so 2 key tissues in the body, the adipose tissue and the skeletal muscle, and we now know that our adipose tissue, and also our skeletal muscle, are highly active in terms of secreting different endocrine or hormonal mediators within the body. Now, they don't show up on this classic textbook diagram of the endocrine system. But it's important to keep in mind that we do have other sites in the body that are also active in terms of their endocrine function. Okay? So a key concept of today's lecture is that I really want to emphasize that our nervous system, which we talked about in last class and interacts with our endocrine system, which we'll talk about in today's class. So the nervous system interacts with the endocrine system to form the foundation of the Ccn. And so there's tremendous integration between these 2 systems. And so, even though we talk about them separately, I want you to keep in mind that they are very much interacting within the biological system. And essentially, what we're talking about here is the interaction between the neurons or the nerves and the hormones. So we've previously talked about the neurohormones. We spend quite a bit of time in the last couple of lectures talking about different neurotransmitters that get released within the nervous system, and they get released by the axon ending or axon terminal of the presynaptic neuron, and then they enter the synapse and then find their receptor on the next neuron postsynaptic neuron. And then that signal gets propagated. But, in fact, there are some nerves that do release their neurotransmitter directly into the bloodstream. And these are what we refer to as neurohormones. So neurotransmitters. Then, instead of hitting the next nerve or acting on the next neuron, they get released directly into the bloodstream, and then they travel to another site within the body. The second point here is that all primary endocrine glands and secondary endocrine tissues in the body are innervated by neurons of the autonomic nervous system. So again, there's this interaction between the nerves or the neurons and the neurotransmitters and our endocrine system, or our endocrine tissues within the body. Remember that neurotransmitters can modulate hormone secretion. So the neurotransmitter when it gets released instead of acting on that next neuron. It enters the bloodstream. It travels to its target site, and then it induces hormone secretion at that site. So a really classic example of this would be norepinephrine, which is a classic neurotransmitter that can then stimulate the release of epinephrine, which is a hormone epinephrine then exerts, its effect which is to suppress the release of insulin, which is another hormone in the body. And so you can see there's this interaction between a neurotransmitter or a neural hormone, and then some of the more classic hormones within the body, such as insulin. To explain this classic example a little bit further, the sympathetic nervous system releases norepinephrine. So it's acting as a neurotransmitter. We know that the norepinephrine gets released during fight or flight situations. So in response to stress and Norepinephrine has its own target effects, so it gets sent out into the bloodstream. It then travels and hits its target. So, for example, it can reach the adrenal glands. And this is where it's going to stimulate the release of epinephrine epinephrine. Then, once it's released, is going to circulate throughout the body, and when it reaches the pancreas. It causes the pancreas to reduce the release of the hormone called insulin. and the last point in the slide here, to make about the interaction between the nervous system and the endocrine system is that neurons in the central nervous system and the peripheral nervous system have many receptors or have receptors for many hormones. So these neurons can also respond to various hormonal influences. For example, these neurons can have receptors for insulin or estrogen or testosterone, and then we get an effect occurring, because those are the target cells expressing, expressing that receptor. And then an effect will be induced. And so the point here is that there really is this strong interaction between our nervous system and our endocrine system, and that this really forms the foundation of the control and communication network or the Ccn. And this is the basis for intercellular communication within the biological system. This is how cells and tissues will communicate with one another. So both the neurotransmitters and neurohormones, and our classic endocrine hormones or hormonal mediators in the body are involved in this interaction or integration. So lots of chemical messengers acting throughout the body forming the basis of the Ccn. okay, so I just want to distinguish here the difference between neurotransmitters and neurohormones. I know we've talked about this already in our discussion a couple of weeks ago with neuroendocrine signaling. But I just want to revisit it here and just include it in your note package. So neurohormones, we said, are neurotransmitters with downstream effects on hormone secretion. So classic neurotransmitters are chemical messengers that are released by neurons that transmit signals to adjacent or nearby cells, and these are often cells within the nervous system or other neurons. They act at synapses. So these neurotransmitters get released into synapses which are the junctions between the neurons or the nerve cells and their target cell. And so this target cell could be another neuron. It could be a muscle cell, or it could be a gland. And so the key point here being that they act on adjacent cells or a nearby cell. On the other hand. Neurohormones are neurotransmitters, that instead of acting at that synapse they get released by the neuron, and then they enter into the bloodstream. So once they've entered the bloodstream. They travel throughout the body to a distant cell or gland, and this is where they exert their effect. And because these neurohormones are entering the bloodstream, and traveling to distant sites, they act more broadly on the body, and they act to influence the function of various endocrine glands that leads to the release or secretion of other hormones. Okay, let's talk a little bit more about where hormones come from in the body. In particular, the pituitary gland. So here on the slide. We have a diagram of the pituitary, and it has different lobes. So we're going to look specifically at the posterior pituitary which is shown here, and the anterior pituitary shown here, and so anterior means the front part of the body or front part of a structure. Posterior means the back part of a structure so opposite to anterior. So we have our anterior pituitary, and then our posterior pituitary. And in fact, it's really only the anterior pituitary. That's a true endocrine gland, and it releases many hormones, and we'll look at that in a couple of slides. The posterior pituitary, on the other hand, isn't really an endocrine gland at all. It's more of a collection of nerve endings that release both oxytocin and antidiuretic hormone or adh into the pituitary's circulation and these hormones have specific functions. Oxytocin has many different functions within the body. In females it's responsible for contraction of the uterus. So it's involved in the birthing process. It's also involved in the ejection of milk from milk producing glands within the body, and oxytocin is our hormone that's also responsible for feelings of love or bonding or bliss. And so you might imagine that between a mother and a newborn infant oxytocin is going to be involved in that bonding or love experience between the mother and that newborn child. It's also involved in positive mood feelings of love, and that's in any individual. So it also has another name of the love hormone. antidiuretic, hormone, or adh, just as the name suggests antidiuresis diuresis means the loss of water, so antidiuresis would be preventing the loss of water antidiuretic hormone acts at the level of the kidney, and it serves to retain fluid or retain water by the kidney, so it prevents the loss of water at the level of the kidney. And so that's what the posterior pituitary releases oxytocin and adh, and they have very specific functions within the body. But, in fact, the posterior pituitary. It doesn't synthesize the oxytocin or the adh. They are actually made elsewhere. So they're made in these neurosecretory cells shown up here in the hypothalamus. And so it's the hypothalamus that's responsible for the synthesis of these hormones, and then they get released, and they travel down to the posterior pituitary. So both adh and oxytocin, then, are basically neurotransmitters that are carried down by nerves into the capillary bed of the posterior pituitary. So you can see here that it's the posterior pituitary where these hormones get released further than into the circulation. So, in other words, adh and oxytocin are neurohormones or neuroendocrine messengers that are released by nerve endings into the circulation, and then they become released by the posterior pituitary, which will then go out through the body and circulate through the bloodstream, where they can exert their actions on various target tissues in the body. And so again, those target tissues being, in the case of oxytocin, the uterus in a pregnant woman, for example, or in the case of adh, the target tissue is the kidney. So it would be correct to say that the posterior pituitary releases these 2 hormones, but it does not synthesize them. They're made higher up by the neurosecretory cells that are found within the hypothalamus and then again traveling through those neurons or nerves down to the capillary bed, and eventually getting to the posterior pituitary, which will release them into the bloodstream so they can travel to their target tissues elsewhere in the body. Now the anterior pituitary is very different. It is, in fact, a true endocrine gland, and it releases many hormones which we'll look at in in a couple of slides. So a practical example here with oxytocin, so oxytocin is the hormone that we said is responsible for contraction of the uterus during the birthing process. It also oxytocin levels also increase in breastfeeding to initiate milk ejection, and we said that oxytocin is the hormone responsible for feelings of love, bliss, and bonding. And because of this it's implicated in social cognition and social behavior. So in the mother, the increase in oxytocin to promote milk. Ejection during breastfeeding also promotes feelings of calmness in the mother. Now, in conditions where oxytocin levels are too low in the body. This is associated with conditions such as autism, spectrum, disorder as well as depression, anxiety, stress. These are all associated with low oxytocin levels as well as higher levels of perceived pain. And so this diagram here shows that the baby suckling sends a signal to the nerves in the hypothalamus up here. This, then, causes the release of oxytocin from the posterior pituitary, which results in milk ejection, as well as some of those other feelings that we've talked about feelings of love and bonding. And so you don't need to worry about the specifics of this diagram here. This is just to show you the stimulus or the mechanism of oxytocin release in the mother. so adh is also called antidiuretic hormone, or also called vasopressin adh, we said, induces the retention of fluid at the level of the kidneys. So it prevents the loss of water. and because of this function of adh, it plays an important role in regulating our blood volume, and therefore our blood pressure. So in response to severe blood loss or dehydration, these both cause a decrease in our blood volume, and therefore a decrease in our blood pressure. And so when this happens, there's an increase of adh release as a mechanism to try to increase water retention and then maintain blood pressure or bring that blood pressure back up to normal levels. So when blood volume decreases, this could be due to severe blood loss, which is called hypovolemic shock. This could be due to an accident or some sort of trauma, or, in the case of severe dehydration. The posterior pituitary will then release adh to promote water retention at the level of the kidneys. And this is an attempt to bring blood volume and blood pressure back to normal levels. Now in heart failure. Adh also plays a role. So in heart failure, the heart becomes weak. It can't pump properly. So there's this decrease in blood flow. And again, a decrease in blood pressure that results as a consequence of this, so as a mechanism to then try and increase blood pressure in response to this adh, then gets released. And so this adh leads to water retention from the kidneys to bring blood pressure back up. But, in fact, what happens with this fluid retention is something called fluid overload, and this can cause a buildup of fluid in the patient's legs, their arms, their lungs, and it actually worsens the symptoms of heart failure. So the release of adh is a mechanism that's trying to help fix this problem of low blood pressure that's caused by heart failure. But it actually tends to make the symptoms of heart failure worse. And this is what we call congestive heart failure, because this results in the buildup of fluid. Again, in the arms, the legs, sometimes the lungs and various tissues in the body. Okay, this is a schematic which shows you the hormones of the anterior pituitary and the anterior pituitary. It does act like a true endocrine gland. It contains endocrine cells that release many hormones. So there is a lot going on with this diagram here. But we're going to walk through it. So I'll draw your attention to this middle bar here, this peach colored bar with the green endocrine cells in the middle. And so this shows you the various hormones that are released from the anterior pituitary. so the green cells in the middle would be the endocrine cells of the anterior pituitary. Then up above. Here in purple, we have control at the level of the hypothalamus in the brain, and then at the bottom, we have our secondary organs or target tissues. These are the target tissues of the hormones released from the anterior pituitary. So 3 levels of sort of complexity in this diagram and 3 levels of control within our body. So the 1st is the hypothalamus in the brain, then the anterior pituitary as part of our pituitary gland, which is that little pea-sized organ at the base of the brain. And then we have our secondary organs or tissues. And so if we walk through this diagram. There's sort of this layering effect here the top level. We can see the neurosecretory cells that are contained within the hypothalamus. Most of these tropic hormones here released by the neurosecretory cells within the hypothalamus. Most of them are positive in the effect that they're going to exert. And that's indicated by the plus signs shown here. There are a few negative tropic hormones indicated by a minus sign, and we'll go through those ones as well. But what I mean by positive is that the tropic hormone that's released from the neurosecretory cells within the hypothalamus. These are going to act positively. They're going to have a positive effect, or promote the release of a certain hormone from the anterior pituitary. So that's what we mean by a positive effect. A negative effect, on the other hand would be the tropic hormone released from those neurosecretory cells in the hypothalamus, would inhibit what happens at the anterior pituitary. So the names of the tropic hormones found within the hypothalamus derive from the effect that they're going to have at the level of the anterior pituitary. So they've been pretty well named. And then I've added to the slide here a list or a legend of what these abbreviations stand for the names of these hormones, and so we'll walk through this together. So if we start at the left-hand side of the slide, here we see prolactin releasing hormone. and then, if we look down at the level of the anterior pituitary. You see that prolactin releasing hormone has a positive effect. To induce the release of the hormone prolactin from the anterior pituitary prolactin is then going to travel in the circulation and find its specific receptor, and it's going to bind to it and exert its effect within the target tissue. So, for example, here one target tissue would be the breasts, and it would induce the growth of breast development in the female prolactin is going to target the breast tissue to stimulate growth, and also the development of lactose production or from milk production. So then, if we move along the diagram here a little bit, we see thyroid releasing hormone in the hypothalamus, which is then going to have a positive effect at the level of the anterior pituitary, to release thyroid, stimulating hormone. and then thyroid, stimulating hormone is going to travel through the blood through the circulation to find its target tissue, which is the thyroid gland, and that will stimulate the release of various thyroid hormones from the thyroid gland. Then moving along, we have crh or corticotropin, releasing hormone, which has a positive effect on the anterior pituitary to release adrenal corticotropic hormone. And this hormone is going to find its target tissue, which is the adrenal cortex, and it's going to stimulate the release of hormones from the adrenal cortex, such as cortisol. So hopefully you can start to see this sort of tiered approach or hierarchy starting in the hypothalamus with the release of a particular tropic hormone. We then get the release of hormones at the anterior pituitary, and then potentially at the target tissue. The release of even more hormones. So the next one we have growth hormone releasing hormone, which has a positive effect on the anterior pituitary to release growth. Hormone and growth. Hormone has actions at various tissues throughout the body, so growth hormone can act by binding to its receptors in the liver to induce the release of insulin like growth factor growth hormone can also find its receptor on various cells throughout the body. We're going to talk about growth hormone a little bit more in the next slide. and then the last one to talk about in terms of the positive tropic hormones we have gonadotropin releasing hormone, and it's going to act positively on the anterior pituitary, to release various gonadotropic hormones. And so these would be things like follicle stimulating hormone or luteinizing hormone, and they'll exert their effects on target tissues, which are the gonads. So in the males this leads to the release of androgens, and in the female this leads to the release of estrogen and progesterone. So again, lots of information here, I do want you to be able to follow each one of these through from the level of the hypothalamus to the anterior pituitary, and then to the target tissue. And what hormones may be secreted at that level of the target tissue. And again, all of the definitions here are provided on the right hand side. So there are also a couple of hormones that work at the level of the hypothalamus that might have a negative effect on the anterior pituitary so shown here we have prolactin inhibiting hormone, which is actually dopamine, and this hormone has a negative effect on the anterior pituitary. And so we have prolactin inhibiting hormone. It's going to inhibit the release of prolactin from the anterior pituitary and as the name suggests prolactin inhibiting hormone again prevent the release of prolactin from the anterior pituitary. There's another example here of an inhibitory hormone. It's growth hormone inhibiting hormone also known as Somatostatin, and since it has a negative effect at the level of the anterior pituitary, it will inhibit the release of growth hormone from the anterior pituitary, and then without growth. Hormone, you would lose some of these downstream effects that growth hormone normally would elicit. So again, do keep in mind. There are both positive and negative tropic hormones at the level of the hypothalamus released from the neurosecretory cells in the hypothalamus, and they either upregulate or downregulate the release of hormones from the anterior pituitary. So hopefully, this gives you some idea of the sort of multi-hormone axis starting with the top layer, the hypothalamus through the second layer, the anterior pituitary, and then to the secondary organs and tissues. Question. yeah, so I do want you to be able to work through each of these examples. So the tropic hormone, released from the hypothalamus. the effect that it has on the anterior pituitary, either going to release a hormone or inhibit the release of a particular hormone, and then the effect that that hormone, released from the anterior pituitary, is going to have on the target tissues, and then, if the effect on these target tissues leads to the secretion of additional hormones. For example, the thyroid hormones or cortisol. Yeah, so I do want you to be able to work through this access for these examples that are on the slide here. okay. So again, the 1st level here being these tropic hormones mainly stimulatory, or have a positive effect. There are some that have an inhibitory effect on the anterior pituitary. The secondary tissues, where these hormones, from the anterior pituitary are going to act can be the breast, the thyroid gland, adrenal cortex, the liver, various cells throughout the body. It could be muscle cells where they're having an effect, as well as the gonads, or the testes, or the ovaries. And so these are all affected. These tissues are all affected by various hormones that are important for controlling or regulating the control and communication network within the Ccn, so very important for communication within the Ccn. okay, I want to take a closer. Look at growth hormone here in particular. And so some of this information we saw on the last slide at the level of the hypothalamus. Up here we have our tropic hormone, which is growth hormone releasing hormone, and this is stimulated by sex hormones and also by deep sleep, and so that can help to regulate the level of growth hormone releasing hormone from the hypothalamus. So we know that growth hormone releasing hormone released from the hypothalamus is going to act on the anterior pituitary to release growth hormone. So growth hormone, then, has various target tissues throughout the body growth. Hormone can act on the liver to induce the release of insulin like growth factor, an insulin-like growth factor is an anabolic hormone, and it's involved in growth and development growth. Hormone can also act on the bone, so the skull and facial bones can be under the influence of growth. Hormone growth. Hormone can also act on the muscle. This is particularly early in life or earlier in growth and development growth. Hormone has a large effect on the muscle to stimulate muscle growth. However, in adulthood there isn't as much of a profound effect of this growth hormone on the muscle. This is really only in cases where growth hormone is administered. In cases where there may be a growth hormone deficiency. So in general providing growth, hormone to an adult does not stimulate muscle growth as much as we might think it would. And then growth. Hormone can also act on the adipose tissue. so we might expect that with a name like growth hormone, the effect is going to be growth enhancing in the adipose tissue, and that is largely what we see with these other tissues. But adipose tissue is an exception, and I will come back to that. And so the effects of growth, hormone on the muscle are early in these stages of growth and in childhood and growth hormone is going to promote protein synthesis, and in the case of the muscle this increase in protein synthesis promotes muscle development, so it has a strong anabolic effect in the muscle. It also has a strong anabolic effect in the bone, promoting the growth and development of bone early in life, and there are a couple of different pictures here, highlighting the effects of growth hormone. So here, on the top left hand corner, this was a previous example of the world's tallest man from the Guinness Book of world records, and so this person would have had an excess of growth hormone. Then, on the other side, we see somebody who may have had a deficiency of growth hormone, and therefore they have stunted growth. and then the effects of growth, hormone excess, or too much growth hormone. They can be seen not just early in life through growth and development, but also later in life. Sometimes tumors can be a trigger of this, so the presence of a tumor might lead to excess production of growth hormone. And so that's what's shown in these pictures on the bottom left hand side here. And so this is the picture of a young woman who had some sort of tumor, and that led to an increase in the release of growth hormone. And so we can see in these pictures with the effects of excess growth, hormone that have sort of spilled over or led into their adulthood. And so this would show up as things like excess bone growth. We can see here the broadening of sort of the nose area that's excess bone growth in the nose as well as excess growth of cartilage, perhaps. and then we can also see sort of the thickening of the nose and thickening of the brow area, and thickening of the jaw, and so these would be the effects of growth hormone in an adult so stimulating the growth of particular bones. And so that's really what can be seen in this picture here on the bottom, left, right at age 33. In this last picture, not totally sure what's happening in that picture. To be honest, it could be some sort of correction of the growth hormone level or hormonal correction, because the symptoms don't seem to be quite as severe here. But again, it's this image at 33. That really shows the change in the skull and the facial bones that are the result of excess growth hormone. And then, as it's noted down here on the bottom of the slide, the skull and facial bones can continue to grow into adulthood with the influence of growth. Hormone, however, this is not the case with the muscle unless it's administered in cases of deficiency, and that's specifically in the adult. Now, the irony here is that if you think about a bodybuilder who might take growth hormone as a means to stimulate muscle protein synthesis, so to build bigger muscles. The muscle is actually not very responsive to growth hormone in adulthood and not as responsive as we might think so. In fact, body builders might anticipate that the administration of growth hormone might help to stimulate muscle growth. But this doesn't actually seem to be scientifically supported. I do want to circle back to the adipose tissue and the effect of growth hormone on the adipose tissue, because it's not what we might think. And so this is one tissue. That sort of goes against the role of growth hormone in terms of growth and development. And so this is one tissue where growth hormone doesn't appear to have a direct enhancing effect. In fact, growth hormone on the adipose tissue or fat tissue, actually promotes the breakdown of fat. and it promotes the breakdown of that fat or that lipid, so that it can provide it as a fuel or energy source for the body, so that growth hormone leads to the breakdown of fat tissue and the release of fatty acids that can then supply the body with energy. And so this may be counterintuitive from what we would normally think in terms of the actions of growth hormone. But it's not contributing to growth of that adipose tissue. It's actually contributing to its breakdown. And so we would call this breakdown of adipose tissue lipolysis or the lysis of lipid, so the breakdown of lipid within the adipose tissue, and when that's broken down and those fatty acids are released into the blood. This provides a really great energy source for the body. And so this sort of feeds into the fact that bodybuilders are quite interested in taking growth hormone for one, because they think that this may stimulate protein synthesis and muscle growth, but it also can inhibit fat growth and promote fat loss within the body. So growth. Hormone might be an attractive hormone for bodybuilders if they're looking for some sort of performance, enhancing effect. and having this sort of fat loss effect or enhancing your lean body mass. So that's a little bit about growth hormone in terms of its effects during growth and development. And what might happen in the case of excess growth hormone. We're going to switch gears here a little bit and briefly look at hormones and some hormone modifying drugs that are used to enhance athletic performance. So again, this is the idea that hormones or hormone modifying drugs can be taken to enhance performance in sport. and so in sport. This is governed by the world, anti doping agency or Wada. And so the symbol for Wada is shown here, and it's meant to indicate an equal sign that represents equity and fairness in sport. The green is meant to stand for health and nature as well as the field of play. And then this play, true tag really sort of encapsulates the core values of Wada, and it's intended to be a guiding principle for all athletes to ensure safe and fair and equitable sport. So the example here on the bottom left hand corner. This is somewhat anecdotal, but this is Barry Bonds. He was a famous baseball player, and there are claims referring to changes in his bone structure and the circumference of his head, it actually increased a full inch. His shoe size increased dramatically, and this was a result of enhanced bone growth from illegally taking performance, enhancing drugs, such as growth, hormone. And so there's a lot of interest in sport, whether it's baseball or other sports, like cycling bodybuilders, or even events in the Olympics, where either growth, hormone, or other hormone modifying drugs or illegal drugs may be used to enhance athletic performance. And so again, Wada governs this very closely, and there are regular drug tests that athletes have to do, and they have to pass these tests to ensure safe, fair, and equitable sport. Okay, so Wada has a list of substances that are prohibited. And so the top here is substances that are prohibited at all times. So both in and out of competition. this list here is somewhat outdated. It's from 2011. I did go back to the website a few days ago to pull the updated list. But it is, in fact, 15 pages long now. And so that's not really the purpose of this. I don't want you to know every single drug that's that's prohibited in and out of sport. So I've just left it as this version here to show you that these are some of the hormones or hormone modifying drugs that we've been talking about, and these would be banned by Wada, and as athletes you would have to adhere or follow these anti-doping guidelines. The list then on the bottom here are hormones or drugs that are prohibited only during competition, so you could use them outside of competition. But if you're in the competing phase, you aren't allowed to use them and so related to today's conversation about hormones and growth hormone. We can see there's peptide hormones, growth factors or growth hormones and related substances listed here that are prohibited at all times in and out of competition. Another one, of course, anabolic androgenic steroids are also prohibited at all times. A classic example of this would be the Canadian sprinter, Ben Johnson. He was caught using anabolic steroids. This was back in the Seoul Olympics in 1988. So before most of our time, and he was caught using this particular banned substance. And then we have Lance Armstrong shown here who I mentioned at the beginning of lecture. He was that famous cyclist who was caught for doping, and he was using a substance that would fall under this s. 2 category, and he was using a substance called erythropoietin, or epo, and so epo is known to stimulate the production of red blood cells. And so with more red blood cells, you can increase the carrying capacity of the oxygen. and so endurance athletes, such as cyclists may turn to something like epo to boost their oxygen, carrying capacity in the blood, and therefore enhance their athletic performance. So Lance Armstrong is sort of the classic example of an athlete who was caught using. Epo. e'll be moving into the local support and defense system. So last day we were talking about the endocrine system as part of the Ccn. Looking at different hormones and the multi-hormone organ access or multi-organ hormone access we ended off last day talking about this list of substances that are prohibited in sport, and this list comes from Wada or the World Anti-doping Agency. So Lance Armstrong, who is pictured here. I mentioned him in last lecture. He was a famous cyclist, and he was caught for doping. He was using a substance that would fall under this s. 2 category, and that substance was called erythropoietin, or epo, and so epo is known to stimulate the production of your red blood cells, and with more red blood cells you can increase the carrying capacity of oxygen in the blood. and so endurance athletes such as cyclists may turn to Epo to boost their oxygen, carrying capacity in the blood, and therefore enhance their performance. So Lance Armstrong is a classic example of an athlete who was caught using. Epo. Now, epo is a hormone that's naturally produced by the kidneys, and it has a very important role to play in the body in terms of red blood cell production. but it can also be artificially produced and injected to enhance performance. Now, Epo has some pretty substantial risks associated with it on top of the fact that it's illegal for performance enhancement. So epo increases your red blood cells, so it increases your blood cellularity, or the number of cells in your blood, and then, during your endurance event, you may become dehydrated. And so there's a large amount of red blood cells, and then you've lost fluid due to dehydration during the athletic event. and this can lead to an increase in the viscosity of the blood, so the blood becomes thicker. It's less watery, and this has been linked with massive heart attack during sport in some of these athletes that are taking epo. So not only is it illegal to use performance enhancing drugs. It's also associated with some pretty severe health risks. And so the point of showing you this is not that you know all of the drugs on this list. It's just to emphasize that we have these hormones as part of our endocrine system with very important roles in the biological system. But there also can be abuse of these substances to enhance athletic performance, so more of an overall concept here, rather than knowing each of these individual drugs that might be on the slide more of an overall concept. So I mentioned anabolic steroid use in relation to the sprinter, Ben Johnson, last lecture, and in addition to being illegal in sport. These anabolic steroids have some very serious and very harmful side effects as well. and so these side effects of using anabolic steroids can often be understated, and anabolic steroids, when they're used in this manner, can have really harmful effects on various tissues and organs in the body. And that's what's shown on the diagram here. So these anabolic steroids are taken with the intention of increasing muscle, tissue, and body mass by acting like the body's natural hormone testosterone. But of course these are drugs, and they have both physical and mental side effects that are associated with them. So they work by mimicking natural testosterone, and the reported effects are increasing muscle, size, and increasing muscle strength, as well as an increase in fat, free body, mass, and all of these are thought to enhance athletic performance. But the list of risks associated with these substances is quite substantial, and really not something that you'd want to mess around with. And so this could involve various cancers or disease in organs such as the liver or the kidneys. It can also involve a heart attack or stroke. severe acne yellowing of the eyes and the skin can also occur. Stented growth. and in males testicular shrinkage can also occur, as well as some behavioral changes, such as depression and violence as well, so a list of potentially severe and harmful effects from taking anabolic steroids. So this slide here some reasons why anabolic steroids or taking growth. Hormone can be harmful in addition to the fact that it's illegal in sport. And so the 1st point, the effective dose that's often taken is super physiological. meaning that you're not taking a dose that's within the normal physiological range in the human body. But you're taking a dose that's much greater than that. And in order for it to be effective, to enhance performance and build that muscle mass. This dose tends to exceed what's considered normal for the human body, and it's not appropriate for the human body, and it can induce these harmful effects. The second point as to why taking particular substances might be harmful is that the dose of the hormone or the hormone agonist that's meant to mimic a particular hormone is generally not timed to mimic or follow our natural hormone production. So remember, the hormones are released according to very complex Circadian patterns, ultradian patterns, Infradian patterns. And we've talked about all of these before we've already mentioned earlier in last day's lecture that the release of growth hormone releasing hormone that leads to the release of growth hormone is promoted by deep sleep. So the growth hormone follows this natural rhythm or pattern within the body. But often, if someone is taking this hormone for enhancing athletic performance, they don't time it to mimic the natural hormone production within the body. And so this graph here shows you the plasma concentration of growth hormone over a 24 h or a 12 h period, and so you can see that sometime here after midnight, which is meant to align with deep sleep the secretion of that growth. Hormone goes up. and so some bodybuilders might take their synthetic growth hormone to mimic their body's natural production of growth hormone. But they also may not do that if they're not aware of this, or if they're not aware of how these hormone levels normally fluctuate in the body throughout the day. so definitely anabolic steroids, growth, hormone. Other substances can be harmful in addition to being illegal in sport. and so that wraps up our discussion on the endocrine system. And we'll switch gears here to look at the local support and defense system. So the local support and defense system here, we're continuing to talk about the Ccn the control and communication network. Remember, the main components of the Ccn are the 2 nervous systems we've now talked about. The endocrine system, and the last component to talk about is the local support and defense system. And so this topic will cover 2 lectures today's and Wednesday's lecture and the local support and defense system. You may think of as the immune system, and in a sense it is. But it does much more than this, and hopefully you'll be able to appreciate that as we go through the lecture today. so when we talk about supporting and defending our body's physiology, it's not just against foreign things that we might come across so things like bacteria, pathogens, or viruses. But it's also our body's way of maintaining the cells and tissues in our body and looking out for any cells that may become abnormal, or may become like a tumor cell or a cancer cell. And so it goes beyond things that are foreign and goes on to support us and defend us on a daily basis. So if we look at the diagram here, we're going to talk about these nonspecific defenses today. The nonspecific defenses come into play first.st And so there's a 1st line of defense and a second line of defense. And very simply put. These would be our basic physical and chemical barriers that block pathogens or anything foreign from getting into the system. The 1st line of defense, in particular, is the nonspecific, physical and chemical surface barriers. An example of this would be our skin, and we'll talk about that in the next slide. Now, if the 1st line of defense fails, we have an intricate line of defense in the second line of defense. And so this is where our internal cellular and chemical defense systems will come into play. And so we'll talk about these today, too. collectively, the nonspecific defenses. So the 1st line of defense and the second line of defense form what we refer to as the innate immune system and the word innate. If you were to look this up means something that is natural, it is not learned through experience. So this innate immune system is just as the name suggests. It's not learned through prior exposure to a particular pathogen. It's very much our nonspecific early 1st and second line of defenses against foreign things that we might come into contact with in our environment if our 1st and our second line of defenses. So if our nonspecific defenses fail, we do have this more intricate immune system, and that is our adaptive immune system. And so it says, this down at the blue box on the bottom. Here. This is our adaptive immune system, or the 3rd line of defense, and this is where our immune responses become quite specific in nature. And so the reason it's called adaptive is because it has a memory, or at least a memory for a certain period of time. And so in this type of system, if there's something specific that you've been exposed to, your immune system, would see it and respond to it. And this might be a T cell response. It might be a B cell response. So making antibodies. And so there would be a corresponding chemical or antibody defense response. And then, the next time that you encounter this Antigen, your immune system would be ready. It would have this memory of being exposed to that previously, and it would be ready to mount a faster, more robust, immune response the next time you encounter that particular antigen or bacteria, for example. So you likely heard about this back when we were in the peak of the covid-nineteen pandemic. So if you had COVID-19, your body developed antibodies to it. and then your body would be able to better defend itself should you come into contact with that covid-nineteen virus a second time. And so your body has that memory against the particular virus or antigen, and it should be able to mount a more robust, immune response the next time that you come into contact with that covid-nineteen virus to then defend against it, or at least lead to less severe symptoms. So today, we're going to focus on these nonspecific defenses. Our innate immune system or the 1st line of defense and the second line of defense. So this is a diagram here that illustrates the 1st line of defense or the external physical barriers that we have in the body to protect us in that 1st line of defense. So part of the innate, immune system. external physical barriers, such as the skin, and also chemical barriers, such as our tears, which contain lysosomes that can kill bacteria that they come into contact with. We also have saliva which can wash away microbes from the teeth as well as mucous membranes of the mouth. So the skin is probably the most obvious in terms of the physical barriers. It's the largest organ in the body, and it provides a physical barrier to the entrance of microbe microbes or pathogens into our body. It's also acidic in nature. So the ph of our skin is, is actually on the acidic side, and this discourages the growth of organisms. We also have various secretions, so sweat or oils that can kill bacteria that we might come into contact with. Then our respiratory system or our respiratory tract plays an important role in the 1st line of defense. So there are mucus secretions within the respiratory tract, and they trap organisms that we might come into contact with. And then we have. These little hair-like projections are called cilia. which will sweep away those trapped organisms. And so, although we might not think about it in this way, the respiratory tract actually does play a really important role as this barrier in our 1st line of defense. Our gastrointestinal system is also really important for defending us against foreign things that we might come into contact with. And so we'll be discussing the gastrointestinal system a bit later in the course. But it is really important that the gi tract or the gastrointestinal system, so our stomach and our large intestine that they have this ability to fight off foreign things or pathogens, that we might come into contact with the stomach is a very acidic environment, and this acid, in addition to helping with the digestion of our food, can also kill certain organisms or pathogens. The large intestine also has its own bacterial population. Many of these are good or healthy bacteria that help to protect us. The host in certain ways. And again, when we get to the section on the Gi tract, we'll be talking more about this. And so this gi tract or Gi system. It's also very important, although we may not think about it in this way, it is very important in that 1st line of defense. Lastly, we have the bladder, so the urine is able to wash away microbes from the urethra. Males have a bit of an advantage here. They have a longer urethra, so they're less susceptible to getting something like a urinary tract infection, whereas females are a little bit more susceptible to urinary tract infections. But nonetheless, this is one of the functions of the bladder and the urine, and that's to wash away microbes so overall lots of external physical barriers and also chemical barriers which act as a deterrent to anything foreign that we might come into contact with in our environment. So the second line of defense we're still talking about our nonspecific or innate immune function that we have in the body. If things were to get past that 1st line of defense, we now have a more intricate system known as our second line of defense, and things do get a little bit more involved here. So we have internal resident cells, various cells that we'll talk about in a minute various defensive proteins that help to protect us, and then we have the ability to produce inflammation in the body and also to develop a fever. And so all of these are part of the second line of defense. The second line of defense basically goes after anything that's foreign or anything that we refer to as non self. And so this is a really key concept. Our immune system has evolved to identify antigens or markers on the cell surface as either belonging to your body, and these are called self, or as being foreign, and these are called non self. And so this happens very early in the development of your immune system. your body learns to accept certain things as self, and to not attack them, and to distinguish them from what's foreign or non-self, and that would be something that the immune system would want to attack. So this idea of self versus non self in terms of the second line of defense. We have various types of defensive cells. So we have phagocytic cells, such as neutrophils and macrophages. We have Xenophills, and we have natural killer cells. And so these would be our primary defensive cells in our second line of defense. And they work through various mechanisms. So neutrophils and macrophages are phagocytic cells. They're known for engulfing and invading organisms. the Xenophylls target parasites in the body and the natural killer cells, or sometimes they're written as Nk cells. They act through secreting various secretions, and they kill invading organisms, various invading organisms. But they're also a very important line of defense for our abnormal or cancerous cells that might arise in the body. And so both the Xenophills and the natural killer cells secrete protein enzymes that are toxic, and they'll kill the target cell or kill the something that they recognize as foreign. whereas phagocytic cells, as their name suggests, their action is to engulf. S