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INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL

INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL. Cérebro Cerebelo Tronco Encefálico. Encéfalo. Mesencéfalo Ponte Bulbo. Sistema Nervoso Central. Medula espinhal. SN. Espinhais Cranianos. Nervos. Sistema Nervoso Periférico. Gânglios Terminações nervosas. Anatomia macroscópica.

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INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL

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  1. INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL

  2. Cérebro Cerebelo Tronco Encefálico Encéfalo Mesencéfalo Ponte Bulbo Sistema Nervoso Central Medula espinhal SN Espinhais Cranianos Nervos Sistema Nervoso Periférico Gânglios Terminações nervosas

  3. Anatomia macroscópica Basal ganglia

  4. Stahl S M, Essential Psychopharmacology (2000) 1-1 ANATOMIA MICROSCÓPICA - NEURÔNIO terminal axon fibers axon cell body dendrites

  5. dendritic spines Stahl S M, Essential Psychopharmacology (2000) 1-2 dendrites spine synaptic vesicles cell body dendrite postsynaptic density axon

  6. Stahl S M, Essential Psychopharmacology (2000) 1-3 presynaptic neuron mitochondrion vesicles postsynaptic neuron synaptic cleft

  7. Stahl S M, Essential Psychopharmacology (2000) 1-10 neurotransmitter (first messenger) bound neurotransmitter receptor second messenger cellular actions

  8. Regulação dos genes por NT ou psicofármacos

  9. first messenger neurotransmitter neuronal membrane receptor second messenger inactive protein kinase activation active protein kinase inactive transcription factor activated “early” transcription factor FOS mRNA Stahl S M, Essential Psychopharmacology (2000) 2--35

  10. mRNA mRNA mRNA Stahl S M, Essential Psychopharmacology (2000) 2-42 Late gene products

  11. Regulação do número de receptores: “Down-regulation” e “Up-regulation”

  12. Stahl S M, Essential Psychopharmacology (2000) 2-43 DOWN REGULATION

  13. Stahl S M, Essential Psychopharmacology (2000) 2-44 UP REGULATION

  14. Stahl S M, Essential Psychopharmacology (2000) 2-45 Down Regulation Up Regulation

  15. TIPOS DE RECEPTORES MAIS FREQUENTES EM SNC

  16. Stahl S M, Essential Psychopharmacology (2000) 2-2 extracellular membrane transmembrane intracellular side view of receptor with seven transmembrane regions

  17. channel Stahl S M, Essential Psychopharmacology (2000) 2-6 Four transmembrane regions = 5 copies of the ligand gated ion channels receptors make a functioning channel

  18. Stahl S M, Essential Psychopharmacology (2000) 2-7 12 transmembrane regions

  19. Stahl S M, Essential Psychopharmacology (2000) 2-13 7 transmembrane region G protein linked 4 transmembrane ligand gated ion channel 12 transmembrane region transporter

  20. INTERAÇÃO FÁRMACO-RECEPTOR

  21. Haloperidol X

  22. Stahl S M, Essential Psychopharmacology (2000) 8-20 GABA site picrotoxin site alcohol site BZ site barbiturate site

  23. = serotonin = sodium = fluoxetine (Prozac) Stahl S M, Essential Psychopharmacology (2000) 2-20 2-21 2-22

  24. Stahl S M, Essential Psychopharmacology (2000) 2-24 = fluoxetine

  25. NEUROTRANSMISSORES

  26. Critérios para identificação dos NT • Síntese no local de liberação • Armazenagem • Presença no espaço sináptico e ação pós-sináptica • Ativação de Receptores • Presença de enzimas inativadoras

  27. AMINOÁCIDOS

  28. Stahl S M, Essential Psychopharmacology (2000) 8-16 GABA IS PRODUCED GLUTAMATE GABA Glu-AD GABA

  29. Stahl S M, Essential Psychopharmacology (2000) 8-17 GABA IS DESTROYED GABA T destroys GABA Metabólito = semi-aldeído succínico GABA transporter

  30. Stahl S M, Essential Psychopharmacology (2000) 8-18 GABA RECEPTORS GABA transporter Baclofen muscimol GABA A receptor GABA B receptor

  31. Stahl S M, Essential Psychopharmacology (2000) 8-20 GABA site picrotoxin site alcohol site BZ site barbiturate site

  32. Stahl S M, Essential Psychopharmacology (2000) 8-21 GABA BZ

  33. Stahl S M, Essential Psychopharmacology (2000) 8-23 GABA BZ GABA BZ HIPERPOLARIZAÇÃO

  34. Stahl S M, Essential Psychopharmacology (2000) 10-21 GLUTAMATE IS PRODUCED Glutamine Transportadores (ASCT2, GlnT, SN1) Glial cell Glutaminase Glutamate Glutamine Glutamine synthase Glutamate GLU (Glutamate)

  35. Stahl S M, Essential Psychopharmacology (2000) 10-22 GLUTAMATE IS REMOVED Glial cell

  36. Stahl S M, Essential Psychopharmacology (2000) 10-23 GLUTAMATE RECEPTORS AMPA receptor NMDA receptor metabotropic receptor kainate receptor

  37. GLUTAMATE RECEPTORS Calcium channel PCP Receptor AMPA Receptor NMDA Cainato Receptor Metabotrópico = 8 LTP

  38. Stahl S M, Essential Psychopharmacology (2000) 10-24 glycine site Mg site (in the ion channel) zinc site PCP site (in the ion channel) polyamine site

  39. ACETILCOLINA

  40. Stahl S M, Essential Psychopharmacology (2000) 12-8 ACETYLCHOLINE IS PRODUCED Glucose CAT Choline AcCoA ACh ACh

  41. Stahl S M, Essential Psychopharmacology (2000) 12-9 ACETYLCHOLINE IS DESTROYED AChE AChE

  42. Stahl S M, Essential Psychopharmacology (2000) 12-10 ACETYLCHOLINE RECEPTORS presynaptic M2 receptor M2 MX N M1 receptor

  43. Acetylcholine Pathways neocortex frontal amygdala Basal forebrain Ch4 Ch1 Ch2 Ch3 hippocampus Nucleus basalis of Meynert Ch1=medial septal nucleus Ch2=vertical nucleus of the diagonal band Ch3=horizontal nucleus of the diagonal band Ch4=n basalis de Meynert (Mediate memory, learning, problem solving, judgement) Loss in NB-Ch4  Alzheimer’s disease

  44. Stahl S M, Essential Psychopharmacology (2000) 12-12 striatum Interneurons involved in regulating motor movements thalamus Medullary Ach neurons Arousal, attention, sleep lateral tegmental area Upper pons/mesencephalon Parkinson

  45. CATECOLAMINAS E INDOLAMINAS

  46. Stahl S M, Essential Psychopharmacology (2000) 5--31 DOPAMINE IS PRODUCED tyrosine transporter DDC TYR DOPA dihydroxyphenylalanine) TOH DA (Dopamine)

  47. DOPAMINE IS DESTROYED Stahl S M, Essential Psychopharmacology (2000) 5--32 (DOPAC - Ácido diidroxifenilacético) MAO DOPAC, HVA Ácido homovanílico dopamine transporter COMT

  48. DOPAMINE RECEPTORS presynaptic autorecptor dopamine transporter D2 D3 D4 D1 D5

  49. Basal Ganglia Nucleus accumbens a Substantia nigra c b hypothalamus d Tegmentum Stahl S M, Essential Psychopharmacology (2000) 10-7 DOPAMINE PATHWAYS

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