정신질환의 신경생물학적 소견

1. 2008년도 인제대학교 의과대학 의학과 2학년 강의 정신질환의 신경생물학적 소견 신경정신과학교실 김 영 훈

2. 신경세포 Neuron and Neuroglia Neuroglia Astrocyte Oligodendrocyte Microglia Ependymal cell Schwann cell

3. 신경원과 시냅스 세포체 축삭돌기 수상돌기 시냅스 신경신호전달 전기신호전달 화학신호전달

4. 신경원과 시냅스

5. 신 경 신 호 전 달

6. Na+ channels close + 50 K+ leaves cell K+ channels open, K+ begins to leave cell Membrane potential (mV) 0 Na+ channels open, Na+ enters cell - 70 During action potential voltage-dependent Ca++ channels permit Ca++ to enter cell Fig 1. Action potential 전기적 신호전달 안정전위 활동전위 탈분극 재분극 과분극

7. 신경세포막

8. 신경전달물질의 종류 1. monoamine neurotransmitters catecholamines : dopamine, norepinephrine, epinephrine indoleamines : 5-HT(serotonin) acetylcholine 2. amino acid neurotransmitters excitatory : L-glutamate, L-aspartate inhibitory : GABA, glycine 3. neuropeptides (neuromodulators) 4. new neurotransmitters ATP, NO, eicosanoids, etc.

9. 신경펩타이드 pituitary peptides : ACTH, alpha-MSH, lipotropin, TSH, GH, prolactin, oxytosin, vasopressin hypothalamic peptides : CRF, TRH, LHRH, somatostatin gut peptides : CCK, gastrin, substance P, VIP opioid peptides : dynorphin, beta-endorphine, enkephalins circulating peptides : angiotensin, calcitonin, glucagon miscellanous : bladykinin, neuropeptide Y, neurotensin, bombesin,etc.

11. 단가아민 신경전달물질 OH CH3 OH C-C- NH2 OH N C C NH2 OH Indoleamine : serotonin Catecholamines : dopamine, norepinephrine, epinephrine

12. Tyrosine DOPA Dopamine Norepinephrine Epinephrine TH AADC DBH PNMT 카테콜아민과 합성 및 대사 효소 MAO COMT HVA MHPG VMA

13. tryptophan 5-hydroxy-tryptophan 5-hydroxy-tryptamine (serotonin) 세로토닌과 멜라토닌 tryptophan hydroxylase AADC MAO 5-HIAA N-acetyl- transferase N-acetyl-serotonin melatonin HIOMT HIOMT : hydroxy-indole-o-methyltransferase

14. AADC TH tyrosine L-DOPA dopamine DOPA : dihydroxyphenylalanaine NE : norepinephrine 3-OMD : 3-O-methyldopa 3-MT : 3-methoxytyramine DOPAC : dihydroxyphenylacetic acid HVA : homovanilic acid TH : tyrosine hydroxylase AADC : aromatic amino acid decarboxylase DBH : dopamine- -hydroxylase PNMT : phenylethanolamine-N-methyl transferase COMT : catechol-o-methyl transferase MAO : monoamine oxidase COMT COMT MAO 3-OMD 3-MT DOPAC MAO COMT HVA AADC TPH NAT HIOMT tryptophan 5OH- tryptophan serotonin N-acetyl serotonin melatonin MAO TPH : tryptophan hydroxylase NAT : N-acetyl transferase HIOMT : hydroxy-indole-o-methyltransferase 5-HIAA Fig 16. Catecholamine and indolamine metabolism 카테콜아민과 세로토닌의 합성과 대사

15. Catecholamines Serotonin and melatonin Tyrosine Tryptophan MAO TH TPH COMT MAO Dopa 5-OH-Tryptophan AADC HVA Dopamine 5-HT (serotonin) 5-HIAA DBH NAT MHPG Norepinephrine N-acetyl serotonin PNMT HIOMT VMA Epinephrine Melatonin

16. 아세틸콜린 Choline Acetyl-CoA CAT Acetylcholine AChE CoA Choline Acetate CAT : Choline-acetyl-transferase AChE : acetylcholine esterase

17. 아미노산 신경전달물질 Excitatory amino acids : EAAs L-glutamate L-aspartate Inhibitory amino acids : IAAs GABA Glycine (?) Neutral amino acids : others

18. Glutamine GABA neuron GABA와 Glutamate Glial cell Glutamic acid GAD GABA Glutamic acid TCA cycle GABA-T GABA GABA Succinic semialdehyde Kreb’s cycle Succinate GAD : glutamic acid decarboxylase GABA-T : GABA transaminase

20. Dopamine

22. Norepinephrine

24. 5-HT

25. 기 저 핵 중 격 뇌 량 대 상 회 시 상 전전두엽피질 시상하부 편 도 청반핵 뇌하수체 해 마 봉 선 핵 세 로 토 닌 수면 호흡 체온 운동 성 식사 불안 환청 우울 자살

27. Acetylcholine

28. Dopamine Dopamine Dopamine Dopamine neuron neuron neuron neuron CCK CCK CCK CCK dynorphin dynorphin dynorphin dynorphin kappa DA DA DA delta enkephalin enkephalin enkephalin Dopamine CCK GABA Neurotensin CCK-R CCK CCK CCK - endorphin endorphin endorphin mu mu GABA GABA GABA Neurotensin Neurotensin Neurotensin Neurotensin-R D2 D2 D2 ? ? ? D2R Neurotensin DA DA DA DA DA DA DA DA DA DA DA DA Fig 7. Modulation of dopamine release 유리

29. 유리

30. COOH NH2 cytoplasm 1 1 2 2 3 3 4 4 5 5 6 6 7 7 8 8 9 9 10 10 11 11 12 12 lumen Vesicular monoamine transporter extracellular intracellular NH2 COOH Plasma membrane monoamine transporter Fig 3. Structure of monoamine transporters 재흡수 reuptake Neurotranmitter Transporters 신경전달물질 전송체

31. 수용체 4 종류

32. Voltage-dependent ion channel N C Ligand-gated ion channel C N C C C N N N C N Fig 9. Two types of ion channel 이온통로

33. Na+ Acetylcholine Acetylcholine 이온통로 수용체 Nicotinic receptor GABAA receptor Cl- benzodiazepine GABA 5 subunits 4 TMDs each Fig 10. Ligand-gated ion channels

34. NH2 204 113 207 COOH GTP • -adrenoceptor adenylate cyclase Fig 13. G-protein coupled receptor and G-protein G- 단백질 수용체

35. N-말단 e 2 113 Asp 세포 외 e 3 e 1 세포막 i 1 i 2 i 3 G-단백질 세포 내 C-말단

36. neurotrophin family 신경성장인자와 효소 수용체 neurotrophin family neurotrophin family neurotrophin family

37. Tyrosine Kinase

38. Receptor dimerization extracellular Ligand • subunit ligand-binding domain tyr tyr p p p p tyr tyr p p tyr tyr ATP ADP Activated protein • subunit tyrosine kinase domain cytoplasmic Fig 12. Tyrosine kinase 효소 수용체

40. 아드레날린 수용체