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2008년도 인제대학교 의과대학 의학과 2학년 강의 정신질환의 신경생물학적 소견 신경정신과학교실 김 영 훈
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신경세포 Neuroglia Neuron and Neuroglia Astrocyte Oligodendrocyte
Microglia Ependymal cell Schwann cell
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신경원과 시냅스 세포체 축삭돌기 수상돌기 시냅스 신경신호전달 전기신호전달 화학신호전달
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신경원과 시냅스
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신 경 호 전 달
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전기적 신호전달 안정전위 활동전위 탈분극 재분극 과분극 Na+ channels close K+ leaves cell + 50
Membrane potential (mV) + 50 - 70 K+ leaves cell Na+ channels close K+ channels open, K+ begins to leave cell Na+ channels open, Na+ enters cell During action potential voltage-dependent Ca++ channels permit Ca++ to enter cell Fig 1. Action potential 안정전위 활동전위 탈분극 재분극 과분극
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신경세포막
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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.
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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.
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단가아민 신경전달물질 Indoleamine : serotonin
OH CH3 OH C-C- NH2 OH N C NH2 OH Indoleamine : serotonin Catecholamines : dopamine, norepinephrine, epinephrine
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카테콜아민과 합성 및 대사 효소 MAO Tyrosine COMT TH DOPA AADC Dopamine DBH
Norepinephrine Epinephrine TH AADC DBH PNMT MAO COMT HVA MHPG VMA
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HIOMT : hydroxy-indole-o-methyltransferase
세로토닌과 멜라토닌 tryptophan 5-hydroxy-tryptophan 5-hydroxy-tryptamine (serotonin) tryptophan hydroxylase AADC MAO 5-HIAA N-acetyl- transferase N-acetyl-serotonin melatonin HIOMT HIOMT : hydroxy-indole-o-methyltransferase
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카테콜아민과 세로토닌의 합성과 대사 tyrosine dopamine L-DOPA 3-OMD DOPAC 3-MT HVA
melatonin N-acetyl serotonin TH AADC NAT HIOMT COMT MAO 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 Fig 16. Catecholamine and indolamine metabolism tryptophan 5OH- TPH 5-HIAA TPH : tryptophan hydroxylase NAT : N-acetyl transferase HIOMT : hydroxy-indole-o-methyltransferase
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Tyrosine Dopa Norepinephrine Dopamine Epinephrine TH DBH AADC PNMT Tryptophan 5-OH-Tryptophan 5-HT (serotonin) N-acetyl serotonin Melatonin TPH NAT HIOMT 5-HIAA HVA MHPG VMA MAO COMT Catecholamines Serotonin and melatonin
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CAT : Choline-acetyl-transferase AChE : acetylcholine esterase
아세틸콜린 Choline Acetyl-CoA CAT Acetylcholine AChE CoA Choline Acetate CAT : Choline-acetyl-transferase AChE : acetylcholine esterase
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아미노산 신경전달물질 Excitatory amino acids : EAAs L-glutamate L-aspartate Inhibitory amino acids : IAAs GABA Glycine (?) Neutral amino acids : others
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Succinic semialdehyde
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
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Dopamine
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Norepinephrine
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5-HT
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세 로 토 닌 수면 호흡 체온 운동 성 식사 불안 환청 우울 자살 기 저 핵 중 격 뇌 량 대 상 회 시 상 전전두엽피질
중 격 전전두엽피질 시상하부 뇌하수체 편 도 해 마 봉 선 핵 청반핵 시 상 기 저 핵 뇌 량 대 상 회 세 로 토 닌 수면 호흡 체온 운동 성 식사 불안 환청 우울 자살
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Acetylcholine
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유리 Dopamine neuron dynorphin kappa DA enkephalin delta CCK-R CCK -
Fig 7. Modulation of dopamine release enkephalin endorphin DA CCK GABA Neurotensin ? - D2 Dopamine neuron mu dynorphin CCK-R kappa delta D2R Neurotensin-R
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유리
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재흡수 reuptake Neurotranmitter Transporters 신경전달물질 전송체 1 2 3 4 5 6 7 8 9
Fig 3. Structure of monoamine transporters 1 2 3 4 5 6 7 8 9 10 11 12 lumen cytoplasm NH2 COOH extracellular intracellular Vesicular monoamine transporter Plasma membrane monoamine transporter Neurotranmitter Transporters 신경전달물질 전송체
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수용체 4 종류
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이온통로 Voltage-dependent ion channel N C Ligand-gated ion channel
Fig 9. Two types of ion channel
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이온통로 수용체 Cl- Na+ Acetylcholine Nicotinic receptor GABAA receptor
benzodiazepine GABA 5 subunits 4 TMDs each Fig 10. Ligand-gated ion channels
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G- 단백질 수용체 -adrenoceptor adenylate cyclase NH2 204 113 207 COOH GTP
Fig 13. G-protein coupled receptor and G-protein
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세포 외 세포 내 세포막 N-말단 C-말단 e 1 e 2 e 3 i 1 i 2 i 3 G-단백질 113 Asp
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신경성장인자와 효소 수용체 neurotrophin family neurotrophin family neurotrophin family neurotrophin family
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Tyrosine Kinase
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효소 수용체 Receptor dimerization extracellular cytoplasmic Ligand subunit
Activated protein tyr p Receptor dimerization Ligand subunit ligand-binding domain tyrosine kinase cytoplasmic extracellular ATP ADP Fig 12. Tyrosine kinase
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아드레날린 수용체
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