Chemical Events At A Synapse PDF

CHEMICAL EVENTS AT A SYNAPSE PREPARED BY: ENGRID MANALOTO  THE SEQUENCE OF CHEMICAL EVENTS AT A SYNAPSE 1. The neuron synthesizes chemicals that serve as neurotransmitters. It synthesizes the smaller neurotransmitters in the axon terminals and synthesiz...

CHEMICAL EVENTS AT A SYNAPSE PREPARED BY: ENGRID MANALOTO  THE SEQUENCE OF CHEMICAL EVENTS AT A SYNAPSE 1. The neuron synthesizes chemicals that serve as neurotransmitters. It synthesizes the smaller neurotransmitters in the axon terminals and synthesizes neuropeptides in the cell body. 2. Action potentials travel down the axon. At the presynaptic terminal, an action potential enables calcium to enter the cell. Calcium releases neurotransmitters from the terminals and into the synaptic cleft, the space between the presynaptic and postsynaptic neurons. 3. The released molecules diffuse across the narrow cleft, attach to receptors, and alter the activity of the postsynaptic neuron. Mechanisms vary for altering that activity. 4. The neurotransmitter molecules separate from their receptors. 5. The neurotransmitter molecules may be taken back into the presynaptic neuron for recycling or they may diffuse away. 6. Some postsynaptic cells send reverse messages to control the further release of neurotransmitter by presynaptic cells.  NEUROTRANSMITTERS At a synapse, a neuron releases chemicals that affect another neuron. Those chemicals are known as neurotransmitters. Most of the rest of the animal kingdom has all or nearly all of the same transmitters that humans have. The oddest transmitter is nitric oxide (chemical formula NO), a gas released by many small local neurons. Nitric oxide is poisonous in large quantities and difficult to make in a laboratory. Yet, many neurons contain an enzyme that enables them to make it efficiently. Many neu rons release nitric oxide when they are stimulated. In addition to influencing other neurons, nitric oxide dilates the nearby blood vessels, thereby increasing blood flow to that brain area Neurons synthesize nearly all neurotransmitters from amino Acetylcholine, for example, is synthesized from cho line, ac ids, which the body obtains from proteins in the diet. which is abundant in milk, eggs, and peanuts. The amino Figure 2.13 illustrates the chemical steps in the synthesis of acids phenylalanine and tyrosine, present in proteins, are acetylcholine, serotonin, dopamine, epinephrine, and pre cursors of dopamine, norepinephrine, and epinephrine. norepinephrine. Note the relationship among epinephrine, People with phenylketonuria lack the enzyme that converts norepinephrine, and do pamine—compounds known as phenylala nine to tyrosine. They can get tyrosine from their catecholamines, because they contain a catechol group and diet, but they need to minimize intake of phenylalanine, an amine group because excessive phenylalanine would accumulate and damage the brain.  NEUROTRANSMISSION Communication between neurons occurs via synapses, which allow the transmission of messages via neurotransmitters. For messages to pass from one neuron to another, neurotransmitters must be released by the presynaptic neuron and bind to receptors on the postsynaptic neuron. When an electrical impulse reaches the end of a neuron, it triggers the release of neurotransmitters from the pre-synaptic neuron's vesicles. The neurotransmitters then cross the synaptic gap and attach to receptors on the postsynaptic neuron. The presynaptic neuron, which releases the neurotransmitters, is distinguished from the postsynaptic neuron, which receives them. The presynaptic endings and vesicles at the end of each neuron contain the neurotransmitters. The transfer of neurotransmitters from the presynaptic neuron to the postsynaptic neuron is called neurotransmission.  AFTER THE NEUROTRANSMISSION The neurotransmitters released from the presynaptic neuron may either excite or inhibit the postsynaptic neuron, telling it to either release neurotransmitters, slow down the release, or stop signaling completely. After neurotransmission, the signal is terminated, allowing the neurons to return to a resting state. When neurotransmitters get released into the synapse, not all are able to be attached to the receptors of the postsynaptic neuron. However, the gap between the neurons needs to be clearer of neurotransmitters at signal termination. Therefore, the neurotransmitters either get broken down by enzymes, diffused away, or re- uptake occurs. Re-uptake is a process whereby neurotransmitters get reabsorbed back into the presynaptic neuron they came from. After this process, they either get restored back into the synaptic vesicles until needed again, or they get broken down by enzymes.  CLASSIFICATION Excitatory neurotransmitters – these types have an excitatory/stimulating effect on the neurons. If a neurotransmitter is excitatory, it will increase the likelihood that the neuron will fire action potential. Examples of these types of neurotransmitter are epinephrine and norepinephrine. Inhibitory neurotransmitters – in contrast to excitatory neurotransmitters, inhibitory neurotransmitters have the opposite effect, inhibiting/hindering the neurons. If a neurotransmitter is inhibitory, it makes the likelihood of the neuron firing action potential will be decreased. Examples of these types of neurotransmitter are GABA and endorphins. Modulatory neurotransmitters – these are often called neuromodulators.If a neurotransmitter is a neuromodulate, this means it can affect a large number of neurons at the same time, as well as being able to influence the effects of other neurotransmitters. Neuromodulators do not directly activate the receptors of neurons but work together with neurotransmitters to enhance the excitatory or inhibitory responses of the receptors. Examples of these types of neurotransmitters are serotonin and dopamine.  MONOAMINES Monoamine neurotransmitters play a crucial role in many psychological behaviors, including decision-making, emotional response, happiness, depression, and reward response. SEROTONIN Serotonin plays a role as a neurotransmitter as well as a hormone. It is important in controlling mood and can affect the happiness levels of an individual. Serotonin is also important for regulating anxiety, appetite, pain control, and sleep cycles. Serotonin is found in the enteric nervous system in the gastrointestinal tract (the gut) but is also produced in the central nervous system in an area of the brain stem called the raphe nuclei. Serotonin is of the inhibitory class of neurotransmitters as it does not stimulate the brain. Instead, it balances out the excessive excitatory neurotransmitter effects. A deficit in serotonin can be linked to depression, sadness, fatigue, suicidal thoughts, and anxiety. It, therefore, plays a role in the underlying cause of many mental health issues. Serotonin syndrome is a condition whereby there is too much serotonin in the brain. This could be caused by a reaction to drugs, leading to symptoms of restlessness, hallucinations, and confusion, and could be fatal.  ADRENALINE Adrenaline, also referred to as epinephrine, is a stress hormone that is secreted into the bloodstream by the adrenal glands. As an excitatory neurotransmitter, it stimulates the central nervous system. However, excessive levels of adrenaline in the bloodstream could lead to high blood pressure, anxiety, insomnia, and an increased risk of a stroke. On the other hand, low levels of adrenaline may result in reduced excitement and inappropriate responses to stressful situations, which can weaken the stress response. NOREPINEPHRINE Noradrenaline, also known as norepinephrine, is a naturally occurring neurotransmitter produced in the adrenal glands, brainstem, and hypothalamus. As an excitatory neurotransmitter, it stimulates the brain and body to take action during times of stress or danger. This chemical plays a crucial role in activating the body's "fight-or-flight" response, which helps improve alertness and concentration. During times of stress, noradrenaline levels reach their peak, but are at their lowest during sleep cycles. However, excessively high levels of noradrenaline can lead to high blood pressure, anxiety, and excessive sweating. Conversely, low levels of this neurotransmitter may result in decreased energy levels, poor concentration, and even depression. DOPAMINE Dopamine is produced in areas of the brain called the substantia nigra, ventral tegmental area, and the hypothalamus, projecting to the frontal cortex and the nucleus accubens (responsible for reward and pleasure) among other areas. Dopamine is both an excitatory and inhibitory neurotransmitter, as well as a neuromodulator, involved in reward, motivation, and addictions. A surplus of dopamine can result in competitive behaviors, aggression, poor control over impulses, gambling, and addiction. As such, addictive drugs can increase levels of dopamine, encouraging the individual to continue using these drugs to get that pleasure reward. A deficiency in dopamine could result in feelings of depression. It is thought that dopamine can also play a role in the coordination of body movements and a shortage can be seen in those with Parkinson’s disease – resulting in tremors and motor impairments.  AMINO ACIDS GAMMA-AMINOBUTYRIC ACID (GABA) GABA is a neurotransmitter that occurs naturally in the body and is responsible for regulating various brain functions. It is present in many brain regions, including the hippocampus, thalamus, basal ganglia, hypothalamus, and brain stem. The primary role of GABA is to regulate anxiety, vision, and motor control. Individuals who have insufficient GABA may experience poor impulse control, which can lead to seizures in the brain. Moreover, a lack of GABA could contribute to mental health problems such as bipolar disorder and mania. Conversely, too much GABA can cause hypersomnia (oversleeping) and a lack of energy. GLUTAMATE Glutamate is another vital amino acid that plays a crucial role in supporting cognitive functions such as memory formation and learning. It's also considered the most abundant neurotransmitter present in the central nervous system. Glutamate functions as an excitatory neurotransmitter, with its receptors found in the neurons and the glia of the central nervous system. Over-activation of glutamate receptors, due to excessive glutamate, leads to excitotoxicity that can kill neurons. This can lead to various serious health conditions such as Alzheimer’s disease, stroke, and epilepsy. In contrast, insufficient glutamate can lead to psychosis, insomnia, concentration problems, mental exhaustion, and even death.  PEPTIDES Peptides are a sequence of amino acids that are bound together by peptide bonds. Proteins, in contrast, consist of multiple peptide subunits and are longer in length. Generally, peptides are defined as short chains of two or more amino acids, although the distinction between peptides and proteins can be arbitrary. Peptides can serve various biological functions within cells, including acting as hormones that can affect other parts of the body when released from cells. Enzymes can break down proteins into shorter peptide fragments. ENDORPHINS Endorphins, an inhibitory type of neurotransmitter, play a crucial role in reducing the transmission of pain signals to the brain and triggering feelings of euphoria. Structurally, they are similar to opioids and function similarly. Typically produced in response to pain within the hypothalamus and pituitary glands, endorphins can also be released when engaging in physical activity, contributing to the phenomenon known as "runner's high." While there are very few reported symptoms of having an excess amount of endorphins, it could result in an addiction to exercise. Conversely, a deficiency in endorphins may cause depression, headaches, anxiety, mood swings, and a condition known as fibromyalgia, which manifests in chronic pain.  PURINES Certain foods and drinks contain purines, which are natural chemicals. When the body breaks these chemicals down, uric acid is created as a byproduct. To reduce uric acid levels, a low-purine diet restricts the consumption of foods and drinks that contain the highest purine content. ADENOSINE Adenosine is a type of neuromodulator neurotransmitter that has the ability to suppress arousal and enhance sleep cycles. It is primarily found in the presynaptic regions of the hippocampus and functions as a central nervous system depressant. However, having consistently high levels of adenosine can lead to hypersensitivity to touch and heat. Conversely, too little adenosine can result in anxiety and sleep disturbances. Caffeine is an adenosine receptor blocker, which means it prevents the adenosine from binding to the receptors. This is why consuming caffeine late in the day can lead to issues with sleeping and is not recommended.  ADENOSINE TRIPHOSPHATE (ATP) ATP, another type of purine, is present in both the central and peripheral nervous systems, and plays a crucial role in several functions. It helps regulate autonomic control, sensory transduction and communication with glial cells. Acting as a carrier of energy, ATP is released by activated neurons and passed on to other active neurons in the brain. In some brain regions, such as the hippocampus and somatosensory cortex, ATP is excitatory. ACETYLCHOLINE Acetylcholine is the only known neurotransmitter of its kind found in both the central nervous system and the parasympathetic nervous system. The main function of this type is focused on muscle movements, memory, and learning, associated with motor neurons.  ADENOSINE TRIPHOSPHATE (ATP) ATP, another type of purine, is present in both the central and peripheral nervous systems, and plays a crucial role in several functions. It helps regulate autonomic control, sensory transduction and communication with glial cells. Acting as a carrier of energy, ATP is released by activated neurons and passed on to other active neurons in the brain. In some brain regions, such as the hippocampus and somatosensory cortex, ATP is excitatory. ACETYLCHOLINE Acetylcholine is a distinctive neurotransmitter found in both the central nervous system and the parasympathetic nervous system. It is primarily responsible for muscle movements, memory, and learning, and is associated with motor neurons.  Excitatory neurotransmitters function to activate receptors on the postsynaptic membrane and enhance the effects of the action potential, while inhibitory neurotransmitters function to prevent an action potential.  DISORDERS ASSOCIATED WITH DEFECTS IN NEUROTRANSMISSION ALZHEIMER’S DISEASE Alzheimer’s disease is a neurodegenerative disorder characterized by learning and memory impairments. It is associated with a lack of acetylcholine in certain regions of the brain. DEPRESSION Depression is believed to be caused by a depletion of norepinephrine, serotonin, and dopamine in the central nervous system. Hence, pharmacological treatment of depression aims at increasing the concentrations of these neurotransmitters in the central nervous system.  DISORDERS ASSOCIATED WITH DEFECTS IN NEUROTRANSMISSION SCHIZOPHRENIA Schizophrenia, a debilitating mental illness, has been linked to high levels of dopamine activity in the frontal lobes, resulting in psychotic episodes among those affected. Treatment for this condition involves the use of dopamine-blocking drugs to ease the symptoms. PARKINSON’S DISEASE The destruction of the substantia nigra leads to the destruction of the only central nervous system source of dopamine. Dopamine depletion leads to uncontrollable muscle tremors seen in patients suffering from Parkinson's disease.  DISORDERS ASSOCIATED WITH DEFECTS IN NEUROTRANSMISSION EPILEPSY Some epileptic conditions are caused by the lack of inhibitory neurotransmitters, such as GABA, or by the increase of excitatory neurotransmitters, such is glutamate. Depending on the cause of the seizures, the treatment is aimed to either increase GABA or decrease glutamate. HUNTINGTON’S DISEASE Besides epilepsy, a chronic reduction of GABA in the brain can lead to Huntington’s disease. Even though this is an inherited disease related to abnormality in DNA, one of the products of such disordered DNA is the reduced ability of the neurons to take up GABA. There is no cure for Huntington’s disease, but we still can treat symptoms by pharmacologically increasing the amount of inhibitory neurotransmitters.  DISORDERS ASSOCIATED WITH DEFECTS IN NEUROTRANSMISSION MYASTHENIA GRAVIS Myasthenia gravis is a chronic autoimmune disease that affects a small percentage of the population. The illness is characterized by fatigue and muscular weakness without atrophy, which stems from an impairment in synaptic transmission of acetylcholine at neuromuscular junctions. Typically, myasthenia gravis occurs when there are antibodies in the bloodstream that block acetylcholine receptors at the postsynaptic neuromuscular junction. This hinders acetylcholine from stimulating nicotinic receptors at neuromuscular junctions, thus inhibiting its excitatory effects. In rare cases, muscle weakness may occur due to a genetic defect in parts of the neuromuscular junction, which is inherited rather than acquired through passive transmission from the mother's immune system at birth or through autoimmunity later in life.  DISORDERS ASSOCIATED WITH DEFECTS IN NEUROTRANSMISSION ANXIETY May reflect reduced activity of GABA, perhaps due to imbalance of endogenous inhibitors, stimulators of the GABA receptor, or both May also involve imbalances in norepinephrine and 5-HT responses SEIZURE DISORDERS Seizures consisting of sudden synchronous high-frequency firing by localized groups of neurons in certain brain areas, perhaps caused by increased activity of glutamate or reduced activity of GABA  THE EFFECTS OF DRUGS MEDICATION SSRIs are used to alleviate symptoms of various conditions such as depression, anxiety, post- traumatic stress disorder, panic disorder, obsessive-compulsive disorder, and phobias. By blocking the reuptake of the neurotransmitter serotonin into the neuron that released it, SSRIs cause a buildup of serotonin in the synaptic cleft. This increases the likelihood of serotonin reaching the receptors of the next neurons. Benzodiazepines are known to reduce nerve signal excitability in the brain, primarily for individuals who suffer from insomnia, anxiety, panic disorder, and some forms of epilepsy. These medications function by increasing the brain's response to GABA, resulting in a calming effect. However, they are only recommended for short-term use, typically a few weeks, since they can have negative side effects, such as increasing anxiety or changing mood and behavior. Antipsychotic medications are usually used to treat the positive symptoms associated with psychosis (e.g., delusions, hallucinations, and paranoia), primarily in those with diagnosed schizophrenia. As those with schizophrenia usually have too much dopaminergic activity, antipsychotics work to antagonize dopamine receptors. Antipsychotics can also be used for individuals with dementia, bipolar disorder, and major depressive disorder.  THE EFFECTS OF DRUGS ILICIT DRUGS Depending on the type, illicit drugs can either slow down or speed up the central nervous system and autonomic functions. Marijuana contains the psychoactive chemical tetrahydrocannabinol (THC), which interacts with and binds to cannabinoid receptors. This produces a relaxing effect and can also increase levels of dopamine. Heroin binds to the opioid receptors and triggers the release of extremely high levels of dopamine. The more that heroin is used, the more likely a tolerance will develop from it, meaning that the brain will not function the way it did before starting the drug. Cocaine is a stimulant drug as it speeds up the central nervous system, increasing heart rate, blood pressure, alertness, and energy. Cocaine essentially gives the brain a surge of dopamine with quick effects. The effects of cocaine do not typically last very long and can make a person irritable or depressed afterward, leading to a craving of more. Ecstasy is a psychoactive drug that works as a stimulant as well as a hallucinogenic. Ecstasy works by binding to serotonin receptors and stimulating them, as well as influencing norepinephrine and dopamine.  THANKS FOR LISTENING