정신질환의 신경생물학적 소견

2008 년도 인제대학교 의과대학 의학과 2 학년 강의

신경정신과학교실 김 영 훈

Neuron and Neuroglia

NeurogliaAstrocyteOligodendrocyteMicrogliaEpendymal cellSchwann cell

신경세포

신경원과 시냅스세포체축삭돌기수상돌기시냅스

신경신호전달전기신호전달화학신호전달

신경원과 시냅스

신경신호전달

Mem

bran

e po

tent

ial (

mV)

+ 50

0

- 70

K+ leaves cell

Na+ channels close

K+ channelsopen, K+

begins to leave cell

Na+ channels open, Na+ enters cell

During action potentialvoltage-dependent Ca++ channels permit Ca++ to enter cell

Fig 1. Action potential

전기적 신호전달안정전위활동전위탈분극재분극과분극

신경세포막

1. monoamine neurotransmitters catecholamines : dopamine, norepinephrine, epinephrine indoleamines : 5-HT(serotonin) acetylcholine2. amino acid neurotransmitters excitatory : L-glutamate, L-aspartate inhibitory : GABA, glycine 3. neuropeptides (neuromodulators)4. new neurotransmitters ATP, NO, eicosanoids, etc.

신경전달물질의 종류

신경펩타이드

pituitary peptides : ACTH, alpha-MSH, lipotropin, TSH, GH, prolactin, oxytosin, vasopressin hypothalamic peptides : CRF, TRH, LHRH, somatostatingut peptides : CCK, gastrin, substance P, VIP opioid peptides : dynorphin, beta-endorphine, enkephalinscirculating peptides : angiotensin, calcitonin, glucagonmiscellanous : bladykinin, neuropeptide Y, neurotensin, bombesin,etc.

단가아민 신경전달물질OH

OH

C

C

NH2

N

C-C- NH2OH

Indoleamine : serotonin

Catecholamines : dopamine, norepinephrine, epinephrine

OH

CH3

카테콜아민과 합성 및 대사 효소

Tyrosine

DOPA

Dopamine

Norepinephrine

Epinephrine

TH

AADC

DBH

PNMT

HVA

MHPG

VMA

MAO COMT

세로토닌과 멜라토닌

tryptophan

5-hydroxy-tryptophan

5-hydroxy-tryptamine(serotonin)

tryptophan hydroxylase

AADC

N-acetyl-serotonin

melatonin

5-HIAAMAO

N-acetyl-transferase

HIOMT

HIOMT : hydroxy-indole-o-methyltransferase

tyrosine dopamineL-DOPA

3-OMD DOPAC3-MT

HVA

melatoninN-acetylserotonin

TH AADC

NAT HIOMT

COMT

COMT

MAO

MAO

COMT

DOPA : dihydroxyphenylalanaine NE : norepinephrine3-OMD : 3-O-methyldopa3-MT : 3-methoxytyramineDOPAC : dihydroxyphenylacetic acidHVA : homovanilic acidTH : tyrosine hydroxylaseAADC : aromatic amino acid decarboxylaseDBH : dopamine- -hydroxylasePNMT : phenylethanolamine-N-methyl transferaseCOMT : catechol-o-methyl transferaseMAO : monoamine oxidase

Fig 16. Catecholamine and indolamine metabolism

tryptophan serotonin5OH-tryptophan

TPH AADC

5-HIAATPH : tryptophan hydroxylaseNAT : N-acetyl transferaseHIOMT : hydroxy-indole-o-methyltransferase

MAO

카테콜아민과 세로토닌의 합성과 대사

Tyrosine

Dopa

Norepinephrine

Dopamine

Epinephrine

TH

DBH

AADC

PNMT

Tryptophan

5-OH-Tryptophan

5-HT (serotonin)

N-acetyl serotonin

Melatonin

TPH

NAT

HIOMT

5-HIAAHVA

MHPG

VMA

MAOCOMT

MAO

Catecholamines Serotonin and melatonin

CholineAcetyl-CoA

Acetylcholine

CholineAcetate

CoA

CAT

AChE

CAT : Choline-acetyl-transferaseAChE : acetylcholine esterase

아세틸콜린

아미노산 신경전달물질

Excitatory amino acids : EAAs L-glutamate L-aspartateInhibitory amino acids : IAAs GABA Glycine (?)

Neutral amino acids : others

GABA neuron

Glial cell

Glutamic acid

GAD

GABA

Succinic semialdehyde

Succinate

GABA-T

Glutamic acid

GABA GABA

GABA 와 Glutamate

GAD : glutamic acid decarboxylaseGABA-T : GABA transaminase

Kreb’s cycle

TCA cycle

Glutamine

Dopamine

Norepinephrine

5-HT

중 격

전전두엽피질

시상하부

뇌하수체 편 도 해 마 봉 선 핵 청반핵

시 상

기 저 핵 뇌 량대 상 회 세 로 토 닌

수면호흡체온운동성식사불안환청 우울자살

Acetylcholine

Fig 7. Modulation of dopamine release

enkephalin

endorphin

DA

CCK

GABA

Neurotensin

?

-

DA

DA

CCK

D2

DA

Dopamineneuron

mu

dynorphin

enkephalin

endorphin

DA

CCK

GABA

Neurotensin

?

DA

DA

CCK

D2

DA

Dopamineneuron

dynorphin

enkephalin

endorphin

DA

CCK

GABA

Neurotensin

?

DA

DA

CCK

D2

DA

Dopamineneuron

Neurotensin

dynorphin

DA

DA

CCK

DA

Dopamineneuron

dynorphin

DopamineCCKGABA

Neurotensin

CCK-R

kappa

mu

delta

D2RNeurotensin-R

유리

유리

Fig 3. Structure of monoamine transporters

1 2 3 4 5 6 7 8 9 101112

1 2 3 4 5 6 7 8 9 1011 12

lumen

cytoplasmNH2 COOH

NH2 COOH

extracellular

intracellular

Vesicular monoamine transporter

Plasma membrane monoamine transporter

NeurotranmitterTransporters신경전달물질 전송체

재흡수reuptake

수용체 4 종류

N

C

N C N CNN

NCC

C

Voltage-dependent ion channel

Ligand-gated ion channel

Fig 9. Two types of ion channel

이온통로

Cl-

GABA

benzodiazepine

Na+

Acetylcholine

Acetylcholine

Fig 10. Ligand-gated ion channels

Nicotinic receptor GABAA receptor

5 subunits4 TMDs each

이온통로 수용체

NH2

COOH

113 204207

-adrenoceptor adenylate cyclaseGTP

Fig 13. G-protein coupled receptor and G-protein

G- 단백질 수용체

세포 외

세포 내

세포막

N- 말단

C- 말단

e 1

e 2

e 3

i 1i 2 i 3

G- 단백질

113 Asp

신경성장인자와 효소 수용체

neurotrophin family neurotrophin family neurotrophin family

neurotrophin family

Tyrosine Kinase

Activatedprotein

tyr

tyr

tyr

p

p

p

tyr

tyr

tyr

p

p

p

Receptor dimerization

Ligand

subunitligand-binding domain

subunittyrosine kinase domain cytoplasmic

extracellular

ATP ADP

Fig 12. Tyrosine kinase

효소 수용체

아드레날린 수용체