Chemical transmission in Nervous system.pptx

Chemical transmission in Nervous system.pptx

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  Chemical transmission in Nervoussystem
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   Neurotransmitters arethe chemical substances liberated at the nerve ending that help to transfer the message in the form of nerve impulse from the presynaptic neuron to postsynaptic neuron.  There is large number of chemicals in the nervous system that act as transmitters. Neurotransmitters
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   Brain Neurotransmitters Chemical substances released by electrical impulses into the synaptic cleft from synaptic vesicles of presynaptic membrane.  Diffuses to the postsynaptic membrane. Binds to and activates the receptors. Leading to initiation of new electrical signals or inhibition of the postsynaptic neuron
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   Classification ofNeurotransmitters:  Amines  Acetylcholine (ACh)  Dopamine (DA)  Norepinephrine (NE)  Epinephrine  Serotonin (5-HT)  Histamine  Amino Acids  Gamma-aminobutyric acid (GABA)  Glycine  Glutamate  Aspartate
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   bradykinin  beta-endorphin bombesin  Calcitonin  cholecystokinin  enkephalin  dynorphin  Insulin  gastrin  Substance P  neurotensin  Glucagon  secretin  somatostatin  motilin
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   Vasopressin  oxytocin prolactin  thyrotropin  Angiotensin II  Sleep peptides  galanin  Neuropeptide Y  Thyrotropin-releasing hormone  Gonadotropnin-releasing hormone  Growth  hormone-releasing hormone  Luteinizing hormone  Vasoactive intestinal peptide
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   Major BrainNeurotransmitters: Ach. Glutamate. GABA Nor epinephrine (NE) Epinephrine. Serotonin. Dopamine
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   Metabotropic: Transmembranereceptor which acts through a secondary messenger.  Ionotropic: Ligand gated ion channel  Cholinergic System:  Acetylcholine is the major neurotransmitter in the peripheral nervous system.  It’s the second most common neurotransmitter in the brain.  In the brain, cholinergic (ACh producing) neurons are present mainly in 2 areas:  Basal Forebrain1 (mainly Nucleus Basalis of Myenert and septal nuclei)  Mesopontine tegmental area which is also called ponto- mesencephalic cholinergic complex Classes of Receptors:
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   Acetylcholine Receptors: Acts on 2 cholinergic receptors: ◦ Nicotinic (ionotropic)  The muscle-type: can be selectively blocked by curare2  The neuronal-type: blocked by hexamethonium3  Excitatory ◦ Muscarinic (metabotropic) (antagonist- Atropine):  Excitatory or inhibitory4  Five subtypes (M1-M5): all are found in the brain but M1 is abundant.  M1 receptors most involved in cognitive functioning (evidence from Knockout mice and pharmacologic human studies with M1 Blocking drugs)  M2 blocking agents may facilitate cognition in animals (but these drugs are not being used in humans at this point).  M3 receptors do not seem to play much of a role in cognition (animal studies).  M4 and M5 functions in the brain are unknown.
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   Learning (highlevels)  Memory (high levels)  Alertness  Thought  Sleep (low levels, except during REM Sleep)  Speed of information processing in the brain  Production of myelin sheath  Muscular coordination Ach Functions
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  ◦ Alzheimer’s Disease:the most common form of dementia Associated with acetylcholine loss Damage to Ach producing cells in the basal forebrain.  Ach levels are disturbed in:  Bipolar disorder (episodes of depression followed by mania “elevated mood”)  Mood swings  Depression  Deficiencies in Ach can lead to myasthenia gravis  Inhibitors of acetyl cholinesterase in the brain are the main drugs used to treat Alzheimer’s disease. Ach Disorders
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   Functions OfGlutamate Glutamic acid (and aspartic acid): are major excitatory NTs in CNS. Learning and memory  Disorders Of Glutamate  Excess Glutamate activity is implicated in some types of epileptic seizures  Under some pathological conditions, such Stroke, ALS (Amyotrophic Lateral Sclerosis)1, autism, and Alzheimer's disease, it acts as an excitotoxin, producing excessive influx of calcium into the neurons and causing neuronal death. GLUTAMATE
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   Presynaptic inhibition GABAA receptors in CNS are chronically stimulated to regulate neuronal excitability.  Disorders of GABA:  under activity of GABA leads to seizures. While over activity of glutamate leads to seizures  Alcohol, barbiturates, progesterone and deoxycorticosterone also in part work by increasing GABA activity Functions of GABAergic System
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  ◦ Norepinephrine (NE):is a catecholamine that is synthesized from Dopamine. ◦ It is released from sympathetic nerves, the adrenal medulla and brainstem neurons. ◦ It acts on both α and β adrenergic receptors (G-protein-coupled receptors) ◦ NE is believed to play a role in both learning and memory. ◦ The Noradrenergic System has a very wide spread projection system ◦ Locus ceruleus is activated by stress and coordinates responses via projections to thalamus, cortex, hippocampus, amygdala, hypothalamus, autonomic brainstem centers, and the spinal cord. ◦ Nucleus Coeruleus is located in the pons, involved in physiological responses to stress and panic. ◦ Locus coeruleus neurons fire as a function of vigilance and arousal ◦ Irregular firing during quiet wakefulness ◦ Sustained activation during stress ◦ Their firing decreases markedly during slow-wave sleep and virtually disappears during REM sleep. Norepinephrine (NE)
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   Functions ofNor epinephrine Withdrawal from some drugs of abuse (NE imbalance + other NTs)  Anxiety and other stress-related disorders such as panic disorder. (High levels of NE)  Sleep Attention/Vigilance  It constitutes part of the RAS (Reticular Activating System)  Fight or flight response (reaches much higher levels during situations of stress or danger)  Learning  Enhances formation and retrieval of memory  Aggressive behavior
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   Depression (decreasedlevels of NE)  Withdrawal from some drugs of abuse (NE imbalance + other NTs)  Anxiety and other stress-related disorders such as panic disorder. (High levels of NE) Disorders of Norepinephrine
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   1. Serotoninis synthesized from the amino acid tryptophan, which is abundant in meat  2. Our bodies cannot make tryptophan (must get from diet)  3. Tryptophan deprivation alters brain chemistry and mood  4. There is only a few 100,000`s of 5-HT neurons in human brain  5. There is 7 classes serotonin receptors in different parts of CNS (most are metabotropic, except 5-HT3)  6. Mice in which the gene for 5-HT2 C receptors has been knocked out are obese. These receptors are responsible for reducing the appetite. If blocked, it may result in obesity Serotonin
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   Improved mood Decrease appetite  Sleep Disorders of Serotonin:  Depression (low levels)  Anxiety (high levels) Drugs (e.g. Prozac “fluoxetine” is a selective serotonin reuptake inhibitor, an antidepressant) that prolong serotonin’s actions, relieve symptoms of depression & obsessive disorders Serotonin (5-HT) Functions
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   Dopamine isa catecholamine that is synthesized from tyrosine.  Five dopaminergic receptors (D1-D5).  Overstimulation of D2 receptors is thought to be related to schizophrenia  Disorders of Dopamine:  Parkinson’s Disease.  Schizophrenia ◦ Cocaine elevate activity at dopaminergic synapses. Dopamine
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