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Brain Neurotransmitters Brain Neurotransmitters Prof. Laila Alayadhi 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 post-synaptic neuron Prof. Laila Alayadhi Prof. Laila Alayadhi 1- Adrenaline / NE 2- Ach 3- Glutamate 4- GABA 5- Serotonin 6- Dopamine Prof. Laila Alayadhi 1- Norepinephrine System Nucleus Coeruleus in the pons, involved in physiological responses to stress and panic Prof. Laila Alayadhi The Locus Coeruleus/Norepinephrine System • Very wide-spread projection system • LC is activated by stress and co-ordinates responses via projections to thalamus, cortex, hippocampus, amygdala, hypothalamus, autonomic brainstem centers, and the spinal cord • Sleep • Attention/Vigilance Prof. Laila Alayadhi 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. Prof. Laila Alayadhi Norepinephrine (NE) Implicated in Stress- Related Disorders • Reduced level in: • Depression • Withdrawal from some drugs of abuse (NE imbalance + other NT) • High level in anxiety panic disorder Prof. Laila Alayadhi PGi: Nucleus paragigantocellularis Prof. Laila Alayadhi PrH: Perirhinal Cortex Prof. Laila Alayadhi 2- Acetylcholine Prof. Laila Alayadhi Major neurotransmitter in the peripheral nervous system Associated with: Thought Memory Muscular coordination Speed of information processing in the brain Production of myelin sheath Prof. Laila Alayadhi ACh influences mental processes High levels during: Learning Memory REM (rapid eye movement sleep) Low levels during: Sleeping (Except REM) Prof. Laila Alayadhi Alzheimer’s Disease- Most common form of dementia Associated with acetylcholine Damage (Ach producing cells in the basal forebrain) Disturbed levels in : Bipolar disorder Mood swings Depression Mental attension Prof. Laila Alayadhi 3- Glutamate It is the most commonly found neurotransmitter in the brain It is always excitatory Important factor in neuronal cell degeneration: Motor neuron disease Huntington's disease Parkinson's disease Alzheimer's disease Prof. Laila Alayadhi Important role in Learning and memory Reduced level in: Stroke Autism Intellectual disability Alzheimer's disease Prof. Laila Alayadhi 4-Gamma Aminobutyric acid (GABA) Inhibitory neurotransmitter of CNS (found in retina) Formed by decarboxylation of glutamate. Three types of GABA receptors e.g. GABAA B & C. GABA A & B receptors are widely distributed in CNS. GABAC are found in retina only GABA B are metabotropic (G- protein) in function. Prof. Laila Alayadhi GABA is the main inhibitory neurotransmitter in the central nervous system (CNS). GABAergic inhibition is seen at all levels of the CNC: Hypothalamus, hippocampus, cerebral cortex and cerebellar cortex GABA interneurones are abundant in the brain, with 50% of the inhibitory synapses in the brain being GABA mediated. Prof. Laila Alayadhi Prof. Laila Alayadhi 5- Serotonin The serotonin pathways in the brain: The principal centers for serotonergic neurons are the rostral and caudal raphe nuclei >>>> axons ascend to the cerebral cortex, limbic & basal ganglia Serotonergic nuclei in the brain stem >>>> descending axons (terminate in the medulla& spinal cord Prof. Laila Alayadhi Serotonin (5-HT) Disorders • Low level in Depression • Anxiety Prof. Laila Alayadhi 6-Dopaminergic Pathways Dopamine is transmitted via three major pathways: 1- The first extends from the substantia nigra to the caudate nucleus-putamen (neostriatum) and is concerned with sensory stimuli and movement. Prof. Laila Alayadhi 2- The second pathway prject to the mesolimbic forebrain Related to cognitive, reward and emotional behavior 3- The third pathway, known as the tubero- infundibular system Rleated to neuronal control of the hypothalmic-pituatory endocrine system. Prof. Laila Alayadhi Dopaminergic Pathways/Functions Prof. Laila Alayadhi Dopaminergic neurons disorders Schezophrenia. Parkinson’s Disease. Prof. Laila Alayadhi Postsynapti Derived Site of Postsynaptic Neurotransmitter Fate Functions c effect from synthesis receptor 1.Acetyl choline Excitatory Acetyl co- Cholinergic 1.Nicotinic Broken by Cognitive (Ach) A + nerve endings 2.Muscarini acetyl functions e.g. Choline Cholinergic c cholinesterase memory pathways of Peripheral action brainstem e.g. cardiovascular system 2. Catecholamines Excitatory Tyrosine Adrenal Excites 1.Catabolized For details refer i. Epinephrine in some produced in medulla and both alpha to inactive ANS. e.g. fight (adrenaline) but liver from some CNS α & product through or flight, on inhibitory phenylalanin cells beta β COMT & MAO heart, BP, in other e receptors in liver gastrointestinal 2.Reuptake into activity etc. ii.Norepinephrine Excitatory Tyrosine, Begins inside α α 1 2 adrenergic Norepinehrine found in axoplasm of β β 1 2 nerve endings controls attention pons. adrenergic 3.Diffusion & arousal, Reticular nerve ending is away from sleep/wake cycle. formation, completed nerve endings to locus inside the body fluid coerules, secretary thalamus, vesicles mid-brain iii. Dopamine Excitatory Tyrosine CNS, D1 to D5 Same as above Sensory motor concentrated receptor Cognetive/emotion in basal ganglia al behavior and dopamine Endocrine pathways e.g. Hypothalamic Prof. Laila Alayadhi nigrostriatal, mesocorticolim Decreased bic and dopamine in Neurotransmitt Postsynaptic Site of Postsynaptic Derived from Fate Functions er effect synthesis receptor 3. serotonin Excitatory Tryptophan CNS, Gut 5-HT1 to Inactivated by Mood control, (5HT) (chromaffin 5-HT 7 MAO to form 5- sleep, pain cells) 5-HT 2 A hydroxyindoleace feeling, Platelets & receptor tic acid(5-HIAA) temperature, BP, retina mediate in pineal body it & hormonal platelet is converted to activity aggregation & melatonin smooth muscle contraction 4. Histamine Excitatory Histidine Hypothalamu Three types Enzyme diamine Arousal, pain s H1, H2 ,H3 oxidase threshold, blood receptors (histaminase) pressure, blood found in cause breakdown flow control, gut peripheral secretion, tissues & the allergic reaction brain (involved in sensation of itch) 5. Glutamate Excitatory By reductive Brain & Ionotropic and It is cleared Long term 75% of amination of spinal cord metabotropic from the brain potentiation excitatory Kreb’s cycle e.g. receptors. ECF by Na + involved in transmissio intermediate hippocampus Three types dependent uptake memory and n in the α – of ionotropic system in learning by brain ketoglutarate. receptors e.g. neurons and causing Ca++ NMDA, AMPA neuroglia. influx. and kainate Prof. Laila Alayadhi receptors. Neurotransmitt Postsynaptic Site of Postsynaptic Derived from Fate Functions er effect synthesis receptor Aspartate & Glycine form an Spinal 6. Aspartate Excitatory Acidic amines Spinal cord excitatory / inhibitory pair in the cord ventral spinal cord GABA – A GABA – A causes increases the hyperpolarization Cl - (inhibition) conductance, Decarboxylati Anxiolytic drugs GABA – B is on of like metabotropic glutamate by Metabolized by benzodiazepine 7. Gama amino Major works with G glutamate transamination to cause increase in butyric inhibitory CNS – protein decarboxylas succinate in the Cl- entry into the acid(GABA) mediator GABA e (GAD) by citric acid cycle. cell & cause transaminase GABAergic soothing effects. catalyzes. neuron. GABA – B cause GABA – C increase found conductance of K+ exclusively in into the cell. the retina. Is simple Glycine Deactivated in Glycine is amino acid receptor the synapse by inhibitory having amino makes simple process of transmitted found group and a Spinal postsynaptic reabsorbtion by in the ventral 8. Glycine Inhibitory carboxyl cord membrane active transport spinal cord. It is group more back into the inhibitory attached to a permeable to presynaptic transmitter to carbon atom Cl- ion. membrane Renshaw cells. Prof. Laila Alayadhi Prof. Laila Alayadhi.
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