Molecular neuropharma


Published on

Published in: Technology
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Molecular neuropharma

  1. 1. NeuropharmacologyNeuropharmacology (Central Nervous(Central Nervous System)System)
  2. 2. Nervous system: Central nervous system (CNS): brain and spinal cord Peripheral nervous system (PNS): cranial nerves and spinal nerves somatic- skeletomuscular sysem autonomic- internal organs sympathetic parasympathetic Two types of cells: neurons and supporting (glial) cells
  3. 3. Types of neurons: Interneuron- located entirely within CNS, integrates functions in CNS Sensory (from sensory receptor to CNS) Motor (from CNS to effector organ) somatic- stimulates skeletal muscles autonomic- affects smooth and cardiac muscle, also glandular secretion Nerve- bundle of neurons (axons) Ganglion- bundle of nerve cell bodies outside of CNS Nucleus- within CNS Tract- connects regions of CNS
  4. 4. Parts of a neuron Cell body- contains the nucleus and other organelles Dendrites- transmit electrical impulses TO the cell body Axon- transmits impulse AWAY from the cell body axons can be several feet long “Axonal hillock” is located near the cell body nerve impulses originate there
  5. 5. Structures of neurons sensory motor retina
  6. 6. Supporting cells Schwann cells, oligodendrocytes- produce myelin Satellite cells- support neurons in PNS Microglia-phagocytes in CNS Astrocytes- induces blood-brain barrier Ependymal cells- special epithelium that line brain ventricles and central canal of spinal cord also part of structure that makes CSF
  7. 7. Large axons are myelinated by Schwann cells or oligodendrocytes Gaps are left between the “wrappings” of each cell (nodes of Ranvier) Myelinated axons conduct nervous impulses more rapidly than unmyelinated In CNS, myelinated axons form “white matter” (Cell bodies and dendrites are gray matter)
  8. 8. Schwann cells can help repair damaged nerves Capacity for repair is much better in the periphery In fetal brain, neurotropins promote neuron growth Some factors help maintain neural structures in adult nervous systems Some inhibitory factors also
  9. 9. Astrocytes Most common glial cell in CNS Form blood-brain barrier Help with ion uptake Help with neurotransmitter uptake Many glucose transport carriers, which help move glucose from blood to brain
  10. 10. Blood-brain barrier (BBB) Probably due to effects of astrocytes on brain capillaries Everything must move into brain by diffusion and active transport Many substances (including therapeutic drugs) cannot cross BBB
  11. 11. Electrical activity in axons Resting membrane potential in neurons is –70 mV Large negatively charged molecules inside the cell Positively charged ions outside the cell (more Na out than K in) Neurons are excitable: they can change their membrane potential in response to stimulation
  12. 12. Permeability to ion changes Occurs in a very small area on the membrane Depolarization- potential difference approaches zero Repolarization- back to the resting potential Hyperpolarization- potential difference increases positive charges leave cell negative charges enter cell
  13. 13. Gated ion channels for K and Na (lots of these at axon hillock) Resting cell is more permeable to K than Na Depolarization- membrane becomes permeable to Na, and Na can diffuse into cell After Na gates close, K gates open and K diffuses out of the cell
  14. 14. Action potentials are very rapid Inactivation occurs until membranes are repolarized (by sodium-potassium pumps) Stronger stimuli stimulate more and more axons (more action potentials are stimulated, but their amplitude does not change)
  15. 15. Refractory period When an action potential is being produced, a second stimulus will not affect that part of the membrane Stimulus when K gates are open and membranes are repolarizing Relative refractory period- a very strong stimulus can overcome repolarizing
  16. 16. Synapse- connection between a neuron and a second cell From presynaptic to postsynaptic neuron Release of neurotransmitters (chemicals) A few electrical synapses in nervous system, In smooth muscle and heart gap junctions
  17. 17. Chemical synapses One-way Presynaptic neuron has synaptic vesicles Fusion of vesicles is mediated by calcium Calmodulin is activated Protein kinase activated Synaptic vesicles fuse with membrane Neurotransmitters diffuse across cleft and bind to receptors
  18. 18. Voltage-regulated channels in presynaptic axon Chemically regulated channels in postsynaptic membrane Ion channels are opened, depolarization occurs Can be excitatory or inhibitory Depends on which receptors are engaged Integration of impulses in dendrites and cell body of postsynaptic neuron
  19. 19. Criteria for establishing a molecule as aCriteria for establishing a molecule as a neurotransmitterneurotransmitter  synthesissynthesis  the molecule is synthesized in the presynaptic neuronsthe molecule is synthesized in the presynaptic neurons  localizationlocalization  the molecule is present in the presynaptic terminalthe molecule is present in the presynaptic terminal  releaserelease  the molecule is released upon stimulation of the presynaptic neuronthe molecule is released upon stimulation of the presynaptic neuron  mimicrymimicry  when applied exogenously (e.g., from a micropipette), inwhen applied exogenously (e.g., from a micropipette), in concentrations similar to those observed following stimulation ofconcentrations similar to those observed following stimulation of the presynaptic cellthe presynaptic cell  the molecule mimics the action of the endogenously releasedthe molecule mimics the action of the endogenously released transmittertransmitter  inactivationinactivation  a specific mechanism or a set thereof exists to remove the moleculea specific mechanism or a set thereof exists to remove the molecule from the synaptic cleft or to degrade itfrom the synaptic cleft or to degrade it
  20. 20. Acetylcholine Excitatory to some neurons in CNS and motor neurons Inhibitory to others Different cells have different types of receptors Nicotinic- stimulatory; nicotine also binds skeletal muscle fibers, autonomic ganglia Muscarinic- muscarine also binds smooth and cardiac muscle; glands
  21. 21. Ion channel most direct type of activation EPSP (excitatory postsynaptic potential) no threshold can be graded (number of stimulated receptors) no refractory period summation: effect of several EPSPs added (i.e., graded)
  22. 22. Muscarinic receptors- operated by G proteins Three subunits to G protein, different ones can be effectors Tends to have in inhibitory effect (IPSP)
  23. 23. Why inhibitory? K+ diffuses out, causing hyperpolarization Both EPSPs and IPSPs can be produced voluntarily- summate or cancel each other out
  24. 24. Acetylcholinesterase (AChE) Inactivates ACh. Otherwise ACh-receptor complexes would keep forming.
  25. 25. In PNS ACh stimulates muscles to contract In ANS: sympathetic and parasympathetic nerves Effect depends on whether nicotinic or muscarinic receptors are activated If EPSPs are above threshold an action potential will be generated along the axon
  26. 26. Monoamines as neurotransmitters Monoamines dopamine norepinephrine serotonin Tend to be stimulatory; must be quickly inhibited to maintain control
  27. 27. Control mechanisms: Uptake of monoamines by presynaptic neuron Degradation by monoamine oxidase in presynaptic neuron By post-synaptic neuron (COMT*, degrades catecholamines) COMT= catechol-O-methyltransferase
  28. 28. Monoamines act through second messenger (cAMP) Catecholamines norepinephrine- hormone and neuro- transmitter controlled by: reuptake monoamine oxidase (MAOIs inhibit this) COMT in postsynaptic neuron
  29. 29. Serotonin derived from tryptophan affects specific cells in brain stem regulates mood and behavior, appetite, cerebral circulation SSRIs- serotonin-specific reuptake inhibitors increase effect of serotonin antidepressants May have different effects depending on receptor
  30. 30. Dopamine dopaminergic cells located in midbrain effects on motor and emotional function Nigrostriatal- motor; in substantia nigra Parkinson’s disease- degeneration of these neurons L-DOPA and MAO inhibitors- increase dopamine transmission
  31. 31. Drugs relieve symptoms for awhile, but do not stop killing of neurons Growth factors? Transplants? (fetal cell, xenotransplants, auto- transplants of carotid body cells, etc.) Areas of research: what exactly is the problem interaction with other neurotransmitters effects on other parts of the brain (in mood, behavior, physical activity, etc.)
  32. 32. Summary 1. The nervous system is comprised of the central nervous system (brain, spinal cord) and the periphery (cranial and spinal nerves) Periphery is divided into autonomic and motor neurons. 2. Cells of the nervous system are glial cells and neurons. Neurons conduct nervous impulses, glial cells “support” neurons. 3. Myelination affects the speed at which impulse is delivered.
  33. 33. 4. Neurons conduct electrical and chemical signaling. Action potential starts at a very small area of the membrane and is conducted along the length of the membrane. Action potential rises with Na influx and falls with K efflux. 5. Speed of transmission is affected by a.) presence of myelin, and b.) the diameter of the neuron. (faster in larger neurons) 6. Neurotransmitters deliver signals across synapses.
  34. 34. 7. Sometimes signal is excitatory, sometimes inhibitory. Excitatory: receptors serve as ion channels, depolarizes, brings closer to threshold. Inhibitory: causes hyperpolarization A given synapse is always one or the other. Some act as second messengers (more long-term effects). 8. Neurotransmitters are typically small fast- acting molecules. Some are larger and slower-acting than others learning, motivation, response to stress, etc.
  35. 35. 9. Long-term potentiation: if a neuron is stimulated once, synaptic transmission is more efficient thereafter May favor use of certain neural pathways: “learning” 10. Some transmitters are inhibitory. Postsynaptic: GABA and glycine Presynaptic: interference with axon interferes with calcium influx