Structure of Neuron Recall the structure of Neuron parts of neuron are i. Cell body (Soma) Control centre of a neuron + Contains cytoplasm with central mitochondria, golgi body, Niss!'s neurofibrils, centrioles, microtubules. Ai Processes a. Dendrite: = Short process, usually multiple, may be single or even absent, NissI's granules are present = Provide input to the cell body in the form of local potential {not action potential] ‘b. Axon: = Single, arises from axon hillock, contains axoplasm and surrounded by axolemma. NissI's granules are absent. = Axons carry information away from cell body in the form of action potential. - Action potential are produced in initial segment i.e. just near the origin of axon. It is because initial segment has lowest threshold. Also Refer to neuro physiology ‘Types of Neurons A.On the basis of function: + Sensory or afferent: Carry input to CNS + Motor or efferent: Transmit output of CNS to periphery. Interneurons or internuncial neurons: Situated in between two neurons and relay information with necessary modification. B.Onthe basis of morphology: |. Based on no. of processes &. Apolar: Having no process eg, Chromaffin cells ‘b. Unipolar: With 1 process eg, Cells ‘mesencephalic nucleus of Trigeminal nerve © Pseudo unipolar: Having 1 axon and cell body attached to axon by a process eg, Cells of Dorsal root ganglion nucleus, granules, of Bipolar: With 2 pr Vestibular ganglia fe. Multipolar: 1 axon and many dendrites eg Purkinje cells of cerebellum . Based on shape + Pyramidal : + Stellate - lil, Based on length of Axon a. Golgi type I neuron: Having long axon Eg peripheral nerves and long fiber tracts in CNS. b. Golgi type If neuron: Having short axon eg. Basket cell List the Nervous Tissue Lipids & Proteins Nervous Tissue Lipids i. Present exclusively in the nervous tissue: Sphingomyelins, cerebrosides, Gangliosides fi, Present in other tissue, but in high amount in nervous tissue: Phosphatidyl phosphatides, Plasmalogens ili, Lipids of myelin sheath: Cholesterol, Phosphatides Nervous Tissue Proteins i. Myelin-forming proteins: Form an essential component of myelin along with lipids. Eg. myelin basic protein, proteolipid protein fi, Neuronal Apoptosis Inhibitory protein (NAIP) + Inhibit cell death ili, Hippocalcin: A neuronal Ca** sensor protein iv, X-linked IAP: Inhibitor of apoptosis like NAIP Functions of Na - K* ATP ase: 4. Describe the function of acetylcholine and Na" ATPase. — [2064] : Its functions are as follows: ses eg, Retina, Cochlea, Fusiform Oval, ete. serine, Insitol Vol. 1 a. Maintains the concentration of Na’ & K* in the ECF & ICF, b. Provides concentration gradient fora secondary active transport to operate eg. in renal tubules ¢. Helps in pumping in & out of other ions. eg, Ca®* in caradiac muscles 11 NES 1 | E> oe \Vol. 4 Prevents excess entry of water In ICF by maintaining low Nat concentration in ICF. Primary active transport of H* jons in gastric glands of stomach (proton pump) Metabolism in Brain __ Brain metabolism accounts for 20% of total metabolism ‘of the body even though brain mass is only 2% of the ‘body mass. Glucose is the sole fuel for brain except during Prolonged starvation. Well fed state Carbohydrate: Brain oxidizes around 140 g glucose per day to CO; & 1,0. Brain has no significant stores of glycogen and sa, it depends on availablity of blood glucose. Only ‘Bucuse can penetrate the blood brain-barrier. The brain's GGLUT-3 transporter is insulin independent. fi, Fat: Brain has no significant stores of TAG, and the oxidation of fatty acids from blood makes little contribution to energy production as fatty acids do not efficiently cross the blood-brain-barrier. i, Early fasting (first few days): Brain continues to use blood glucose exclusively as a fuel. Blood glucose is maintained by hepatic gluconeogenesis from glucogenic Precursors such as amino acids from rapid proteolysis of muscle proteins & glycerol from lipolysis. iv. Prolonged fasting (> 2-3 weeks) : Plasma ketone bodies reach significantly elevated levels, & replace glucose as the primary fuel for the brain. This allows the brain to use-body fat (as ketone body is produced |. from acetyl-coA) as a source of energy & reduces the need for protein catabolism for glucogenesis. v. Ammonia toxicity in brain in prolonged-fasting Due to increased NH," levels, increased amount of a - ketoglutarate combine with NH,* & so, a-ketoglutarate is depleted from Kreb’s cycle resulting in decreased production of ATP that causes fluid & electrolyte balance leading to brain swelling, blurring of vision, convulsions, coma & death. Ammonia Removal by Brain i Soil ety + In brain tissue, major mechanism for detoxification of ammonia is glutamine formation. Glutamate + NH tana, ADP +p, seems r am # However, if blood Nib levels are elevay of blood glutamate available to brain i form glutamine. So, the brain must ie ay I mea, glutamate from a- ketoglutarate. _ NH arketoglutarate — aw NADPH+H* ——Napp+ Biochemical basis for ammonia toxicity i. Impairment of TCA cycle [NADPHSH NADP | ecketoglutamate_ A. ce Gutanae + Accumulation of ammonia shits te equilibrium to the right with more Glutamate formation: utilization of & ketoglutarate. ie, more * Depletion of a-ketoglutarate impairs the TC cycle. The net result is that production of enetsy § reduced. li, Decreased GABA [Gamma amino butyric 2041 level Increased concentration of ammonia + More glutamate directed to glutamine syathess | ‘ | Less glutamate available for GABA Sy™S® | 4 Low GABA level + No inhibitory action EE || eer! |iis increased serotonin level Increased concentration of { ammonia | 4 | Increased formation of glutamine | + |_ Increased entry of tryptophan into the brain in | exchange for glutamate | 4 Increase level of tryptophan | t Increased serotonin synthesis (Also refer to general biochemistry for further details on metabolism) Multiple sclerosis & Myelin destruction 4 Muluple sclerosis is an autoimmune demyelinating disease 4 Theloss of myelin is due to the loss of both phospholipids & sphingomyelin from white matter/ myelin sheath, + Hence, lipid composition of white matter resembles that of gray matter + CSF shows raised phospholipid levels and bands of immunoglobulin. igoclonal + Available evidence indicates that disease is initiated b THI cells that secrete IFN-y to activate macrophages, and TH17 cells that promote leukocytes recruitment, which react against myelin antigens. * Exact mechanism of development of demyelination is not ear but may be either due to destruction by the immune system or failure of the myelin-producing cells. Causes may be genetic or environmental factors (eg infection) Neuron and Synaptic Transmission ‘Refer to neuro physiology 1. Describe briefly about the biosynthesis & degradation of acetyl choline in myoneural junction [2068] 2 Describe the mechanism of synthesis of acetylcholine, its function and degraiatlet Neuromuscular junction, (20e3) cy Ust the chemical exe Hatory neurotransmitter, Fxplain GANA (ye aminobuty transmitter, ee SEs (2050) Short answer on Inhibitory action of hosphate polson, {2059} 5. Role of Calum in the release of Neurotransmitters from axon terminal Explain the major blochemtcal derangement in Organophosphate potsoning, Describe the function of [2059 Acetylcholine b. Acetylcholinesterase 8. Define presynaptic end of synapses, [2056] 9 Shortnotes @. Synapses 2067 ». Neurotransmitter and classification 2076, 2072,2071 ©. Synaptic Vesicles 2067 4. Acetylcholine 2064 €. Synaptic Vesicle 2064 f. Acetylcholine (2065, 2062) & Dopamine, Noradrenalineand Adrenaline [2065] h. Energy metabolism in brain [2064] i. Synthesis and degradation of Acetylcholine in neuromuscular junction, [2064] j. Neurotransmitter [2064,2063, 2061] Kk. Synapse [2061] 1. Action potential [2061] m., Depolarisation [2061] ‘n, Opening and Closing of lon Channels[2065, 2061] 10.Write short notes on: [2076] Neurotransmitter 11. Outline the synthesis of acetylcholine and GABA neurotransmitters How do they affect the post- synaptic membrane? (1#142=)4 [2078] INEUROTRANSMISSION STEPS, 1, Synthesis of ACh: from choline and Acetyl CoA by acetyl CoA transferase enzyme 2, Storage of ACh in vesicles: By energy dependent H*- antiporter called vesicular ACh transporter. 111 ERSTE ES 111 EEE Vol. 1Cissus On arrival of action potential presynaptic terminals depolarized, and voltage gated Ca chanels open which cause fusion of vesicles membrane with presynaptic terminal cell membrane and release of ACh. 4, Action of ACh on nicotinic and muscarinic ‘on postsynaptic terminal 5. Termination of ACh action: by Acetylcholinesterase 3. Release of ACh: receptors Neurotoxins Inhibitors of sodium channel are: 1. Tetradotoxin produced by puffer fish ii, Saxitoxin produced by a marine dinoflagellate + Both of these block Na* channels but have no effect on K+ flow . Both contain positively charged guanidinium group which competes with Na+ for interaction with negatively charged carboxylate group at extracellular entrance of the Nat channel. So, Na+ channel loses its ability to transport Na+. + Functions of Acetylcholineste, present in the post-synaptic hydrolyses Acetylcholine into g hence, helps in terminating the ‘at the synapse. Organophosphates phosphorylate Acetylcholinesterase enzyme ang." ty inhibit It producing muscarin (rere x Fase: | euton, holine an, m scion of, eat r central actions. Meat Inhibitory function of snake y, eNom: Describe the function of acetyig inhibitory function of snake venom, alae 2. Describe inhibitory function otro enon pa 067 3. Shortnotes on snake venom e072, The snake venom (a-bungarotoxin) binds iy 7 subunit of acetylcholine receptor. Hence i acetylcholine from binding to the receptor eee inhibiting the response of neuroimpulses and hen post-synaptic tissues (nerve oF muscle) cannot uy impulse conduction is blocked. depolarization, thus, | 1, Explain the mechanism of action of snake venom, kaon [e07 Jy toxic saliva produced by mali n gland) in poisonous snakes. 2. Inhibitory function of snake venom, # Snake venom ish salivary gland (¥ # Snake uses the venom for paralysing the prey digestion and defence Classified on basis of affected organ : a. Blood toxin b. Cardiotoxin © d. Neurotoxin Blood toxin : + Destroys basement membrant Cell toxin and ental matrix E> | || SE ainterferes with blood clotting cqntiotoxty pecreases cardiac output cetttoxin causes tissue necrosis because of thelr protease action Neurotoxin: “interferes with Ach transmission at NM junction _ Canlead to respiratory paralysis and death, needy neurotoxin Ach binding to Kiting Ss tahtated by et —< rardkase t © MAO and COMT are responsible for its degradation Tyrosine, ETF 7 hydroxylase bora catvoxyl Frome Vaniiile Acid anillyl Mandellic Acid Goan pamine " henylethanolam creaming -amethytranterane iiyiroxylasd 2. Histamine: Found in mast cells, basophils Metabolite of = dopa and do © Metabolite of most catacholamines le Diagnosis neuroblastoma © Useful in diagnosis of} pheochromocytoma Other Neurotransmitters : 1, Serotonin(5- HT) Foramtion: L- Tryptophan Tryptophan hydroxylase 5 yy Amino Acid decarboxylase Found in enterochromaffin cells in GIT Degradation: MOA. SH 5-HIAA aldehyde dehydrogenase (Hydroxy indole Acetic Acid) Uses: = Regulation of sleep, memory, appetite and mood. Vol. 1 my L-histidine Nistidine—fecarboxylase? Mstamine It Is degraded by enzyme histamine . y, transferase uy Allhistamine receptors are GPCRs Mediator during inflammation, increases tes, permeability aoa LESTe Tae)