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Basic neurochemistry


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Basic neurochemistry

  1. 1. Basic Neurochemistry Presented by:- Mr. Dharmesh Kheni Training team 1
  2. 2. CONTENTS• Organization of NS• Brain• Spinal cord• Peripheral nervous system• Autonomic nervous system• Neurotransmission• Major neurotransmitters and receptors 2
  4. 4. Brain 4
  5. 5. The Neuron 5
  6. 6. The NeuronSoma Dendrites Myelin Sheath Axon Axon Terminals 6
  7. 7. The Neuron• Soma (cell body) – contains nucleus, cytoplasm, organelles• Dendrites – receive info• Axon – transmits info• Myelin sheath – covers the axon to increase transmission speed (cause of sensory and motor disturbances in multiple sclerosis) 7
  8. 8. Neuron• Basic functional unit of nervous system• Unique features of neuron: – Excitability – Conductivity 8
  9. 9. What is a synapse?• A synapse is the junction between 2 neurones.• There is a very narrow gap of about 20nm between neurones called the synaptic cleft.• A nerve impulse cannot cross the synaptic cleft, so nerve impulses are carried by chemicals called neurotransmitters. 9
  10. 10. SYNAPSE 10
  11. 11. Action Potential/Impulse conduction• The information in neuron is passed from one to another in the form of nerve signal i.e. Action potential, which is due to its unique features of excitability and conductivity. 11
  12. 12. Action Potential• Nerve signals are transmitted by action potential• Any stimulus - Mechanical Physical Biochemical Sudden change in resting membrane potential C 12
  13. 13. 13
  14. 14. Resting membrane potential• Normally there is an excess of positive charges outside the cell• Inside of the cell is negative with respect to outside• Called as Resting membrane potential Normal Resting Membrane Potential is -70mv Due to unequal no. of ions on either side of the membrane 14
  15. 15. Resting membrane potential• Following are the ions which play important role in generating resting membrane potential : - Sodium ions ( +vely charged) - Potassium ions ( +vely charged) - Chloride ions ( -vely charged) - Organic ions ( e.g. proteins) :-vely charged 15
  16. 16. Resting membrane potential• Na+K+Pump actively pump 3 Na+ outside the neuron for each 2 K+ inside the neuron.• Thus Most of the sodium ions remain outside of the cell and Potassium ions are inside the cell.• This creates negative potential inside the resting neuron -70mv 16
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  18. 18. Action PotentialResting stage : - 70mv Any stimulus – Mechanical, Physical or Biochemical Change in resting membrane potential (from -70mv to +30mv) This change in RMP causes opening of voltage gated Na+ channel More entry of Na+ inside the neuron Reaches Maximum electropotential +30 to 35mv This gradual increase in charge is called as depolarization 18
  19. 19. • Depolarization: Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential• Repolarization : After depolarization the action potential ends with equally rapid change back to negative potential 19
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  21. 21. The Synapse • Axon terminal releases neurotransmitters. • Neurotransmitters cross the synapse and bind to receptors on another neuron. • Neurotransmitters released, taken up again by first neuron. 21
  22. 22. NEUROTRANSMITTERS• Chemicals produced by the body that are released from the nerve endings• Enable passage of impulses from one neuron to another across the synapse• Act on their specific receptors (glycoprotein structures on the cell membrane) 22
  23. 23. Neurotransmitter C 23
  24. 24. Fate of Neurotransmitter Pre Synaptic neuronRe u pt ak rs e it te Ch sm a n nn tra e o ur ls MAO Ne Auto Receptor Vesicles torsCOMT apt ic Recep Post Syn Post Synaptic neuron Diffusio n of NTs 24
  25. 25. 1.Fate of Neurotransmitter Pre Synaptic neuron Post Synaptic neuron 25
  26. 26. 2.Fate of Neurotransmitter Pre Synaptic neuronReuptakechannel Post Synaptic neuron 26
  27. 27. 3.Fate of Neurotransmitter Pre Synaptic neuron Auto Receptor prevents further release Post Synaptic neuron 27
  28. 28. 4.Fate of Neurotransmitter Pre Synaptic neuronReuptake MAO Auto Receptorchannel prevents further releaseCOMT Post Synaptic neuron 28
  29. 29. 5.Fate of Neurotransmitter Pre Synaptic neuronReuptake Auto Receptorchannel prevents further releaseCOMT Post Synaptic neuron 29
  30. 30. 6.Fate of Neurotransmitter Pre Synaptic neuronReuptake Auto Receptorchannel prevents further release Post Synaptic neuron Diffusio n of NTs 30
  31. 31. Neurotransmitters• Excitatory : - Stimulate neurons e.g. Noradrenaline, Dopamine, Histamine, Serotonin, Glutamate etc.Acetyl-choline (neuromodulator)• Inhibitory : - Suppress the neurons e.g. GABA (Gamma-Amino-Butyric- Acid) 31
  32. 32. Neurotransmitters• Acetylcholine – movement (respiratory paralysis)• Serotonin – mood, sleep, appetite, anxiety (depression, obsessive-compulsive disorder, panic disorder)• Dopamine – motivation, pleasure (schizophrenia, Parkinson’s)• Epinephrine and Norepinephrine – attention, anxiety, stress (epilepsy, mania in bipolar disorder) 32
  33. 33. Serotonin• Serotonin - 5-Hydroxytriptamine• Also known as 5-HT• Known to control impulse, emotion & behaviour• Increased levels leads to aggression• Reduced level may induce suicidal thoughts• Involved in sleep & depression 33
  34. 34. Serotonin Receptors• The serotonin receptors are called 5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6 & 5HT7.• These are further subdivided as 5HT 1A, 5HT2A,5HT1B, 5HT1D etc. 34
  35. 35. Serotonin Receptors 35
  36. 36. Serotonergicpathways 36
  37. 37. AcetylCholine• Acetylcholine is the major neurotransmitter which controls various activities like1. contraction of skeletal muscles,2. relaxation of cardiac muscles, arousal,3. reward,4. memory,5. short term learning 37
  38. 38. Acetylcholine• Found in neuromuscular junction• Involved in muscle movements 38
  39. 39. Receptors of Acetylcholine• The receptors of Ach are of various types & are complicated in nature• Muscarinic & nicotinic receptors are important• Muscarinic receptors M1, M2, M3 …M5• Binding of Ach with M1 M3 M5 causes stimulatory effects whereas binding with M2 & M4 Causes inhibitory action. 39
  40. 40. Muscarinicreceptor 40
  41. 41. NicotinicReceptor N1, N2 41
  42. 42. Cholinergicpathways 42
  43. 43. Norepinephrine/Noradrenaline• Noradrenaline normally produces effects such as increased heart rate, increased blood pressure, dilation of pupils, dilation of air passages in the lungs and narrowing of blood vessels in non-essential organs. This enables the body to perform well in stressful situations. Increases levels of energy, interest & Mood. 43
  44. 44. Norepinephrine/Noradrenaline• Receptors : Alpha receptors: - α1 receptors Found in the blood vessels - α2 receptors (Auto receptor) Beta receptors: - β 1 receptors Mainly found in heart - β 2 receptors Mainly found in bronchi 44
  45. 45. Noradrenergicpathways 45
  46. 46. DOPAMINE• Dopamine interacts with receptors on some peripheral nerve fibers and many central neurons (eg, in the substantia nigra, midbrain, ventral tegmental area, and hypothalamus).• After release and interaction with receptors, dopamine is actively pumped back (reuptake) into the nerve terminal. 46
  47. 47. Dopamine• Involved in movement, attention and learning, drive, desire motivation & pleasure/reward• Dopamine imbalance also involved in schizophrenia• Loss of dopamine- producing neurons is cause of Parkinson’s Disease 47
  48. 48. DOPAMINE RECEPTORS• Dopaminergic receptors are classified as D1 through D5.• D3 and D4 receptors play a role in thought control (limiting the negative symptoms of schizophrenia); D2 receptor activation controls the extrapyramidal system. 48
  49. 49. D2 is primarily a post synaptic receptorwhereas D3 is believedTo be a autoreceptor 49
  50. 50. Dopaminergicpathways 50
  51. 51. Gama Amino Butyric Acid• It is primarily an inhibitory neurotransmitter responsible for Sleep, prevents anxiety & stress signals & has an overall calming effect on the brain.• It has three receptors GABAA, GABAB & GABAC 51
  52. 52. GABA receptorcomplex 52
  53. 53. Gabanergicpathways 53
  54. 54. SUBSTANCE-P• Substance P, a peptide, occurs in central neurons (habenula, substantia nigra, basal ganglia, medulla, and hypothalamus) and is highly concentrated in the dorsal root ganglia.• Its release is triggered by intense afferent painful stimuli. 54
  55. 55. NITRIC OXIDE• Nitric oxide (NO) is a labile gas that mediates many neuronal processes.• It is generated from arginine by NO synthase, an enzyme that activates soluble guanylate cyclase by binding to Ca/calmodulin complexes.• Thus, neurotransmitters that increase intracellular Ca (eg, substance P, glutamate, acetylcholine) stimulate NO synthesis in neurons that express NO synthetase.• NO may be an intracellular messenger; it may diffuse out of a cell into a 2nd neuron and produce physiologic responses (eg, long-term potentiation [a form of learning], neurotransmitter release and reuptake) or enhance glutamate (NMDA) receptor-mediated neurotoxicity. 55
  56. 56. Glutamate & Aspartate• They are excitatory neurotransmitters.• Their receptors are of 2 types. – Ionotropic – N- Methyl D- Aspartate. (NMDA)Alpha-amino-3-hydroxyl-5-methyl-4-isoxozole propionic acid (AMPA) – MetabotropicTrans-1-aminoclycopentane1,3Dicarboxylicacid. (Trans- ACPD) 56
  57. 57. Drugs• Drugs which have molecules of similar shape to transmitter substances can affect protein receptors in postsynaptic membranes.• Drugs that stimulate a nervous system are called AGONISTS• Drugs that inhibit a nervous system are called ANTAGONISTS. 57
  58. 58. NEUROTRASMISSION• A neuron generates and propagates an action potential along its axon, then transmits this signal across a synapse by releasing neurotransmitters, which trigger a reaction in another neuron or an effector cell (eg, muscle cells; most exocrine and endocrine cells).• The signal may stimulate or inhibit the receiving cell, depending on the neurotransmitter and receptor involved. 58
  59. 59. Blood brain barrier: A mechanism thatcreates a barrier between brain tissues andcirculating blood; serves to protect the centralnervous system. Propagation: passing of electrical impulse within neuron by exchange of Na+ and K+ across the axonal membrane. 59
  61. 61. Receptors• Specific macromolecular components of the cell which act as a binding site with functional correlate to produce effect• Situated - on the surface / inside the cell 61
  62. 62. Drug at Receptor• Agonist : It activates a receptor to produce an effect similar to that of the physiological signal molecule• Antagonist : It prevents the action of an agonist on a receptor but does not have any effect of its own• Partial agonist : It activates a receptor to produce sub maximal effect but antagonises the action of full agonist. 62
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  65. 65. Competitive antagonist– Competes with an agonist for receptors– High doses of an agonist can generally overcome antagonist 65
  66. 66. PHARMACODYNAMICS• It it the quantitative study of the biological and therapeutic effects of drugs.• “What Drug does to the body” 66
  67. 67. PHARMACOKINETICS• It is the study of absorption, distribution, metabolism and excretion of drugs• “What Body does to the Drug” 67
  68. 68. Pharmacokinetics• Absorption How the drug is moved into blood stream from the site of administration ?• Distribution How much drug is moved to various body tissues / organs ? Depends on blood flow through tissue• Metabolism How the drug is altered – broken down ?• Elimination How much of the drug is removed from the body ? 68
  69. 69. Absorption and Bioavailability• Absorption is the movement of drug from its site of administration into the circulation.• Bioavailability : Fraction of administered dose of a drug that reaches the systemic circulation in the unchanged form. – Bioavailability of IV route : 100 % 69
  70. 70. Bioavailability 70
  71. 71. Half-Life• It is a time required for 50% of elimination of the plasma concentration of the administered drug. 71
  72. 72. Half Life (t1/2)110100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 T ime (ho ur s ) 72
  73. 73. DRUG EXCRETION• Kidneys• Lungs• Skin• Bile• Milk and Saliva 73
  74. 74. FACTORS MODIFYING THE EFFECTS OF DRUG • Body weight • Age • Gender. • Diet & environment • Route of administration • Emotional Factors 74
  75. 75. FACTORS MODIFYINGTHE EFFECTS OF DRUG• Genetic factors• metabolic disturbances• Presence of disease• Other drug therapy• Additive effect• Antagonism - chemical antagonism 75
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  77. 77. Effect of nicotine and atropine 77
  78. 78. The Blood-Brain Barrier 78
  79. 79. The Blood-Brain Barrier• Endothelial cells in blood vessels in the brain fit closely together• Only some molecules can pass through• Protects the brain from foreign molecules and hormones and neurotransmitters from other parts of the body• Can be damaged by infections, head trauma, high blood pressure, etc. 79
  80. 80. The Brain 80
  81. 81. The Brain 81
  82. 82. The Brain• Cerebral Cortex – thought, language, reasoning, movement, sensation• Corpus Callosum – connects the right and left hemispheres• Cerebellum – movement, balance• Brainstem – breathing, heart rate 82
  83. 83. Lobes of the Brain 83
  84. 84. Lobes of the Brain• Frontal Lobe – personality, planning, emotion, problem solving – Motor cortex - movement – Broca’s area – speech production• Parietal Lobe - touch• Temporal Lobe – hearing – Inferotemporal Cortex – object recognition – Wernicke’s area – language comprehension• Occipital Lobe - vision 84
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