Podcast
Questions and Answers
What characterizes excitatory neurotransmitters?
What characterizes excitatory neurotransmitters?
How is acetylcholine synthesized in the neuron?
How is acetylcholine synthesized in the neuron?
What is the primary role of dopamine in the central nervous system?
What is the primary role of dopamine in the central nervous system?
Which neurotransmitter is primarily affected in Parkinson's disease?
Which neurotransmitter is primarily affected in Parkinson's disease?
Signup and view all the answers
What effect does botulinum toxin (Botox) have on acetylcholine?
What effect does botulinum toxin (Botox) have on acetylcholine?
Signup and view all the answers
Which of the following is NOT a function of norepinephrine?
Which of the following is NOT a function of norepinephrine?
Signup and view all the answers
What condition is associated with autoantibodies to nicotinic acetylcholine receptors?
What condition is associated with autoantibodies to nicotinic acetylcholine receptors?
Signup and view all the answers
What methods are involved in the inactivation of neurotransmitters?
What methods are involved in the inactivation of neurotransmitters?
Signup and view all the answers
Which receptor type is linked with regulating the release of dopamine?
Which receptor type is linked with regulating the release of dopamine?
Signup and view all the answers
What happens when dopamine increasing drugs are suddenly stopped?
What happens when dopamine increasing drugs are suddenly stopped?
Signup and view all the answers
Which enzyme synthesizes epinephrine from norepinephrine?
Which enzyme synthesizes epinephrine from norepinephrine?
Signup and view all the answers
What is one of the key roles of serotonin in the body?
What is one of the key roles of serotonin in the body?
Signup and view all the answers
Which catecholamine is primarily associated with mania?
Which catecholamine is primarily associated with mania?
Signup and view all the answers
What is the main neurotransmitter in postganglionic neurons of the sympathetic nervous system?
What is the main neurotransmitter in postganglionic neurons of the sympathetic nervous system?
Signup and view all the answers
What effect does increased serotonin activity have on mood?
What effect does increased serotonin activity have on mood?
Signup and view all the answers
What is the primary role of glutamate as a neurotransmitter?
What is the primary role of glutamate as a neurotransmitter?
Signup and view all the answers
Which receptor types are primarily inhibitory for serotonin?
Which receptor types are primarily inhibitory for serotonin?
Signup and view all the answers
What is a common effect of low serotonin levels?
What is a common effect of low serotonin levels?
Signup and view all the answers
What neurotransmitter is derived from the Kreb’s Cycle and plays a role in Alzheimer’s disease?
What neurotransmitter is derived from the Kreb’s Cycle and plays a role in Alzheimer’s disease?
Signup and view all the answers
Study Notes
Neurotransmitters
- Chemical messengers synthesized in neurons, released upon neuronal excitation (dependent on calcium influx).
- Can create excitatory or inhibitory responses in cells or tissues.
- Act on postsynaptic, post-ganglionic, or target cells (effectors).
- Communication mechanism between neurons via chemical synapses.
- Photoreceptors are the only nerve cells active during hyperpolarization.
Functional Classification
- Excitatory: Depolarization.
-
Inhibitory: Hyperpolarization.
- Photoreceptors are the exception.
- Direct (ionotropic): Neurotransmitter binds to ionotropic receptor, channel opens. Neurotransmitter released into synaptic cleft, causing an immediate response.
-
Indirect (metabotropic):
- Neurotransmitter binds to metabotropic receptor.
- G protein-coupled receptor activated and binds to effector protein.
- Second messenger molecules (cyclic AMP, adenyl-cyclase, or phospholipase c) produced, activating enzymes that open channels.
- Neurotransmitter (first messenger) released into synaptic cleft.
Neurotransmitter Inactivation
- Degradation by enzymes: From the postsynaptic cell or within the synaptic cleft.
- Reuptake: By glial cells (astrocytes) or the presynaptic cell.
- Diffusion: Away from the synapse through the bloodstream.
Acetylcholine (ACh)
- Excitatory in skeletal muscle, but inhibitory in cardiac muscle.
- Acetyl-CoA source: Glycolysis products (pyruvate), converted by pyruvate dehydrogenase.
- Acetylcholine is synthesized from acetyl-CoA and choline by choline acetyltransferase (ChAT), the rate-limiting step.
- ACh is packaged into vesicles by a vesicular acetylcholine transporter (vAChT).
- Acetate source: Acetyl-CoA.
- Choline source: Reuptake after cholinesterase enzymatic degradation.
Dopamine (DA)
- Monoamine Oxidase (MAO) and Catechol-O-methyltransferase (COMT): Inactivate DA in the liver, presynaptic or post-synaptic terminal (reuptake-2).
Norepinephrine (NE)
- A catecholamine.
Serotonin (5-HT)
- An indoleamine.
- Dietary tryptophan serves as a substrate for serotonin synthesis.
- Aromatic amino acid decarboxylase: Essential enzyme for serotonin synthesis.
Glutamate
- Derived from amino acids.
-
Sources:
- Kreb's cycle: α-oxoglutarate converted to glutamate by α-oxoglutarate transaminase.
- Reuptake of Glu: Glial or presynaptic cells, or glutamine conversion.
Acetylcholine (ACh) Secretion
-
Location:
- CNS: Cerebral cortex, hippocampus, brainstem.
- PNS: NMJ of skeletal muscle, all preganglionic (sympathetic and parasympathetic) and parasympathetic postganglionic fibers of ANS.
Cholinergic-Acetylcholine Receptors
-
Nicotinic:
- N1 (NM): At the NMJ of skeletal muscle.
- N2 (NN): Autonomic ganglia, CNS, and adrenal medulla (for catecholamine release).
-
Muscarinic:
-
M1 through M5: Widely distributed in the CNS.
- M1: Autonomic nervous system, striatum, cortex, and hippocampus.
- M2: Autonomic nervous system, heart, intestinal smooth muscle, hindbrain, and cerebellum.
-
M3: Mediates pupil constriction and activation of lacrimal gland secretion.
- Pupil constriction: CN 3.
- Lacrimal gland: CN 7.
-
M1 through M5: Widely distributed in the CNS.
Acetylcholine Associated Effects
- Organophosphate insecticides: Prolonged effects of ACh leading to tetanic muscle spasms.
-
Botulinum toxin (Botox): Inhibits ACh release.
- Bacteria: Clostridium botulinum.
- Alzheimer's disease: Decreased ACh levels in certain brain areas.
- Myasthenia Gravis: Nicotinic ACh receptors destroyed.
-
Atropine: Anti-muscarinic cholinergic drug to treat medical conditions like bradycardia, uveitis, and early amblyopia in children.
- Stimulates pupil dilation (mydriasis) and paralyzes the accommodation reflex (cycloplegic).
Alzheimer's Disease (AD)
- Cholinergic neurons of the basal forebrain are involved in learning and memory.
- Characterized by neural atrophy in the cortex and hippocampus, and loss of cholinergic neurons in the nucleus basalis of Meynert.
- Symptoms: Memory loss, personality changes, dementia.
- Treatment (replacement therapy): Donepezil (Aricept), Galantamine (Razadyne ER).
Huntington's Disease/Chorea
- Degeneration of ACh and GABA containing neurons.
- Symptoms: Chorea (sudden, unexpected and purposeless contractions of proximal muscles), dementia.
- Atrophy of the brain basal ganglia and lateral ventricle enlargement.
- Juvenile HD: < 20 years, faster progression.
- Other symptoms: Muscle rigidity, slow or unusual eye movements, walking/posture problems, speech/swallowing deficits.
Myasthenia Gravis
- Autoimmune syndrome with auto-antibodies to nicotinic ACh receptors (N1/NM related to the neuromuscular junction).
- Auto-antibodies reduce the number of receptors at the NMJ.
- Symptoms: Paresis (weakness of voluntary movements).
- Affects extraocular and eyelid muscles (diplopia and ptosis).
- Affects bulbar muscles (nasal speech and jaw fatigue).
- Leads to weaker limbs proximally and stronger limbs distally.
-
Diagnosis test: IV edrophonium (short-acting anticholinesterase drug).
- Muscle use results in fatigue (Tensilon test). If muscle strength increases, likely to have myasthenia gravis.
Lambert-Eaton Myasthenic Syndrome (LEMS)
- Autoimmune disease at the NMJ.
- Immune attack of voltage-gated calcium channels at presynaptic nerve endings, decreasing ACh release.
- Symptoms: Weakness on limb muscles (weak contraction).
- 50% associated with neoplasms (lung, breast, prostate).
- Associated with ANS dysfunction (involuntary), most commonly dry mouth.
Dopamine Receptors
- A catecholamine.
-
Function: Excitatory or inhibitory depending on the receptor type bound.
- Indirect action via second messengers.
-
Location:
- CNS: Sustancia nigra (pars compacta) (SNpc) and VTA of midbrain, hypothalamus (arcuate nucleus) (control energy metabolism in peripheral tissues).
- PNS: Some sympathetic ganglia.
- D4R: Wide functions in the amygdala, hippocampus, pituitary, and retina.
- D1R: Working memory (short-term memory related to thinking and speaking).
- D3R: Addiction behaviors.
- Structurally G-protein-coupled receptors or adrenoreceptors classified as D1 through D5.
-
D1-like receptors (D1R and D5R): Linked to Gs, activate adenylyl cyclase (AC).
- Location: Limbic system, corpus striatum, thalamus, and hypothalamus; mesenteric and renal blood vessels.
-
D2-like receptors (D2R, D3R, D4R): Linked to Gi/Gs, inhibits AC and Ca2+ channels, and activates K+ channels.
- Location: Limbic system, corpus striatum, thalamus, and hypothalamus, pituitary gland; cardiac mm., sympathetics of the heart.
Supplements that affect Dopamine levels
- Receptor AGONISTS: Yohimbine, Ningdong granules.
- Receptor ANTAGONISTS: L-theanine, Ginkgo biloba, Bacopa, Mucuna pruriens.
- High DA levels: Tics, involuntary movements, euphoria, hallucinations, and psychosis.
- Low DA levels: Parkinson's disease.
Dopamine Effects
- A “feeling good” neurotransmitter.
- L-dopa treatment: In Parkinson’s disease.
- Amphetamines: Enhance DA levels.
- Plays a role in cognitive, motor, and neuroendocrine functions.
- Increased production in schizophrenics.
- Mainly controls movements and pleasure.
- In the nucleus accumbens (receives inputs from the VTA), dopamine modulates behavior by reinforcing learning and evading aversion stimuli.
Dopamine Imbalance
Dopamine Clinical Correlation: Parkinson's Disease
- Degeneration of dopaminergic neurons in the substantia nigra (reduced DA release in caudate/putamen).
- Symptoms: Hand tremors, rigidity, akinesia (loss of voluntary muscle movement), dementia.
- Treatment: L-DOPA and carbidopa (inhibitor of dopa-decarboxylase).
Dopamine Clinical Correlations: Psychotic Disorders
- Most common: Schizophrenia (increased activity at dopaminergic synapses).
- Treatment: Phenothiazines, butyrophenones (reduce DA synaptic activity in the limbic forebrain).
Dopamine Clinical Correlations: Cocaine Drug Abuse
- Local anesthetic drug that inhibits the reuptake of DA and NE into nerve terminals.
- Responsible for the euphoric effects.
- DA projections from the VTA to the NAcc (involved in emotional reinforcement and motivation associated with cocaine drug addiction).
Dopamine Boost by Drugs-Abuse
- Illicit drugs: Heroin, cocaine (crack and powder), crystal meth, ecstasy (MDMA derivative), pure MDMA, bath salts, marijuana, LSD.
- Legal drugs: Alcohol, prescription painkillers, benzodiazepines, caffeine.
- Prolonged use: Responsible for withdrawal symptoms after quitting these drugs.
Norepinephrine (NE)
- A catecholamine.
-
Function: Excitatory or inhibitory depending on receptor type bound.
- Indirect action via second messengers.
- Pathway of catecholamines biosynthesis: Dopamine, NE, and E come from the biosynthetic pathway of phenylalanine and tyrosine amino acids.
-
Location:
- CNS: Brainstem (pons)- locus coeruleus nuclei (A6 group of neurons), limbic system, some areas of cerebral cortex.
- PNS: Main neurotransmitter of postganglionic neurons in the sympathetic nervous system.
- FEF: Responsible for saccadic eye movements for VF perception and awareness, as well as for voluntary eye movement.
NE Effects
- May play a role in the genesis and maintenance of mood.
- Amphetamines: Enhance NE release.
- Catecholamine hypothesis: Reduced norepinephrine activity is related to depression, increased NE activity is related to mania.
Epinephrine (E)
- E synthesis occurs in the same way as NE.
- PNMT: Enzyme that converts NE to E.
- E origin: Synthesized in neurons or adrenal medulla, transported back to neurons or used in tissues.
- C1 neurons: Rostral ventrolateral medulla.
- C2 neurons: Nucleus tracts solitarius or solitary nucleus.
Serotonin (5-HT)
- An indoleamine.
- Dietary tryptophan serves as a substrate for serotonin synthesis.
- Function: Mainly inhibitory, indirect action via second messengers, direct action at 5-HT receptors.
-
Location:
- CNS: Brainstem (dorsal and medial raphe nuclei): midbrain, medulla, pons.
- Projections to: Hypothalamus, limbic system, cerebellum, pineal gland (serotonin synthesized here, precursor of melatonin), spinal cord.
Serotonin Receptors
- Receptor families from 5-HT1-5 with family subtypes.
- Receptor types 1, 5, and 6: Inhibitory receptors.
- Receptor types 2, 3, and 4: Stimulatory receptors.
- Second messenger for all families: Cyclic AMP (cAMP).
Serotonin Effects
- May play a role in sleep, appetite, nausea, migraine headaches, regulation of mood, body temperature.
- Low 5-HT levels: Associated with severe depression and insomnia (e.g., Prozac, blocks reuptake of serotonin).
- High 5-HT activity: Associated with mania.
- Obsessive-compulsive disorder: Related to a dysfunction of 5-HT.
- Tricyclic antidepressant and fluoxetine (Prozac): Increase 5-HT availability, relieving anxiety and depression.
- Selective serotonin receptor agonists (for 5-HT10): (e.g., sumatriptan (Imitrex)) can abort migraines due to a vasoconstrictive and anti-inflammatory effect.
Glutamate
- Derived from amino acids.
- Function: Excitatory neurotransmitter.
-
Sources:
- Kreb's Cycle: α-oxoglutarate is converted to glutamate by α-oxoglutarate transaminase.
- Reuptake: Glial or presynaptic cells, or glutamine conversion.
-
Effects: May play a role in Alzheimer’s disease (AD), and the loss of neurons by overexcitation and glutamate-induced activation of NMDA receptors.
- Namenda: NMDA receptor antagonist as a treatment for AD.
-
In retina: Turn on or off photoreceptors related to glutamate circuits.
- Activation of photoreceptors and mGluR6: At night, rods are on and activated by mGluR6, and cones are off at the same time.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
