CAJ | 학술논문

杏仁体中的多巴胺(DA)和γ-氨基丁酸(GABA)递质系统均参与精神分裂症的病理过程,临床上一般用多巴胺Ⅱ型受体(D2)阻断剂予以治疗.然而,目前尚不清楚GABA与D2受体是否共存,也不清楚DA能神经末梢与GABA能神经元之间的联系方式.本实验用共聚焦激光扫描显微镜(CLSM)和免疫电镜(IEM)研究了杏仁体关键性核团基底外侧核中GABA与D2受体的共存关系以及DA神经能末梢与GABA能神经元之间的突触关系.CLSM显示由谷氨酸脱羧酶(GAD)标记的GABA能神经元全部对D2受体呈免疫阳性反应,表明GABA能神经元含有D2受体.IEM显示,在980个DA能神经末梢形成的突触中,45%的突触是由DA免疫反应阳性神经末梢直接(36%)或间接(9%)与GAD免疫反应阳性神经元的树突形成,另55%是由DA免疫反应阳性神经末梢与未标记的神经元成分形成.DA-GABA的直接性突触进而可区分为单突触(16%)、汇聚突触(14%)及轴-轴突触(6%).而DA-GABA的间接性突触是个突触复合体.在该复合体中,DA免疫反应阳性末梢在一个未标记的末梢上形成对称性突触,而该未标记末梢又与GAD免疫反应阳性树突形成非对称性突触.在DA与未标记神经元成分之间的突触中,AD免疫反应阳性末梢分别与未标记胞体(4%)、树突(42%)及轴突末梢(9%)形成突触.所有DA突触无一例外均为对称性突触.本研究结果提示,用于治疗精神分裂症的D2受体阻断剂可能是作用于AM中GABA能神经元而起到削弱DA的传递作用.进而,本研究结果为理解正常及精神分裂时AM中的DA神经通路提供了形态学基础.
행인체중적다파알(DA)화γ-안기정산(GABA)체질계통균삼여정신분렬증적병리과정,림상상일반용다파알Ⅱ형수체(D2)조단제여이치료.연이,목전상불청초GABA여D2수체시부공존,야불청초DA능신경말소여GABA능신경원지간적련계방식.본실험용공취초격광소묘현미경(CLSM)화면역전경(IEM)연구료행인체관건성핵단기저외측핵중GABA여D2수체적공존관계이급DA신경능말소여GABA능신경원지간적돌촉관계.CLSM현시유곡안산탈최매(GAD)표기적GABA능신경원전부대D2수체정면역양성반응,표명GABA능신경원함유D2수체.IEM현시,재980개DA능신경말소형성적돌촉중,45%적돌촉시유DA면역반응양성신경말소직접(36%)혹간접(9%)여GAD면역반응양성신경원적수돌형성,령55%시유DA면역반응양성신경말소여미표기적신경원성분형성.DA-GABA적직접성돌촉진이가구분위단돌촉(16%)、회취돌촉(14%)급축-축돌촉(6%).이DA-GABA적간접성돌촉시개돌촉복합체.재해복합체중,DA면역반응양성말소재일개미표기적말소상형성대칭성돌촉,이해미표기말소우여GAD면역반응양성수돌형성비대칭성돌촉.재DA여미표기신경원성분지간적돌촉중,AD면역반응양성말소분별여미표기포체(4%)、수돌(42%)급축돌말소(9%)형성돌촉.소유DA돌촉무일예외균위대칭성돌촉.본연구결과제시,용우치료정신분렬증적D2수체조단제가능시작용우AM중GABA능신경원이기도삭약DA적전체작용.진이,본연구결과위리해정상급정신분렬시AM중적DA신경통로제공료형태학기출.
Although both dopamine (DA) and γ-aminobutyric acid (GABA) systems in the amygdala (AM) are involved in schizophrenia which is generally treated by administration of D2 receptor antagonists, it is not clear what is the collocation relationship between GABA and D2 receptors and what are the synaptic relationships between the dopaminergic terminals and GABAergic neurons in AM. Present study examined the coexistence of GABA and D2 receptors and synapses formed between dopaminergic terminals and GABAergic neurons in a key nucleus, the basolateral nucleus (BL), of rat AM by means of double labeling immunofluorescent confocal laser scanning microscopy (CLSM) and immunoelectron microscopy (IEM). CLSM revealed that the glutamic acid decarboxylase (GAD) immunolabeled GABAergic neurons were exclusively immunoreactive (IR) to D2 receptors. This indicates that all of the GABAergic interneurons bear D2receptors. IEM revealed that 45% of the DA synapses ( n = 980) were formed between the DA-IR terminals and GAD-IR neurons, and 55% of that formed between DA-IR terminals and unlabeled neuronal elements. In the DA-GABA synapses, the DA-IR terminals targeted either directly (36%) or indirectly (by serial synapse, 9% ) on GAD-IR dendritic structures. Furthermore, the direct DA-GABA synapses could be classified into single ( 16% ) , convergent ( 14% ) and axoaxonic (6%) types according to the number of synapses and the synaptic compositions. In the indirect case, the connection was a synaptic complex, in which a DA-IR terminal formed a synapse on another terminal that form the synapse on the GAD-IR dendrite. In the synapses of DA-unlabeled neuronal elements, the DA-IR terminals targeted on unlabeled perikarya (4%), dendrites (42%), and axons or terminals (9%). Interestingly, all of the DA synapses were exclusively symmetric. The present results suggest that D2 receptor antagonists might act on GABAergic neurons to weaken the DA neurotransmission in AM for clinical effects in schizophrenia. Beyond this, our data provide an anatomical basis for understanding the DA neural circuit in the BL of AM both in normal and schizophrenic conditions.