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신경아교세포와 조현병

Neuroglial Cells and Schizophrenia

원승희
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2015.05|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제22권 제2호|pp. 47-54

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키워드

조현병Schizophrenia병태생리Glial cellTherapeutic target신경아교세포치료 표적Patholphysiology
주제분류정신과학

초록

중추신경계에는 신경세포보다 더 많은 여러 형태의 신경아교세포들이 있으며 신경세포와 상호작용을 통하여 뇌 발달및 뇌 기능에 중요한 역할을 담당한다. 희소돌기아교세포(oligodendrocyte)는 축삭을 둘러싸는 수초를 형성하여 효율적인 신경전달이 가능하도록 하고, 별아교세포(astrocyte)는신경세포와 주변의 혈관을 구조적으로 지지해 주며 신경전달물질을 조절하고 신경영양인자(neurotrophic factor)나 사이토카인을 분비한다. 미세아교세포(microglia)는 면역반응을통해 대뇌의 항상성을 유지한다.1) 최근에는 대뇌 전반에 분포하면서 뇌 부위에 따라 분화가 달라지는 전구세포(progenitor cell)의 일종인 nerve/glial antigen 2(NG2) 양성 세포가신경아교세포에 포함되었다.2) 대부분의 신경과 질환이나 퇴행성 뇌 질환의 병리와 비교하여 조현병의 중요한 차이점 중 하나는 특정 뇌 부위(전두엽, 두접엽, 측두엽, 해마, 부해마회)에 용적은 감소하지만 신경세포의 소실은 관찰되지 않는다는 사실이다.3) 조현병 환자들을 대상으로 실시한 뇌 영상과 사후부검 및 동물모델 연구 결과 뇌 백질의 다양한 이상 소견이 보고되면서, 신경 연결성(neural connectivity) 또는 신경망 연결성(neural networks connectivity)의 단절이라는 구조적 변화에 관심을 가지게 되었고, 뇌 백질을 주로 구성하고 있는 신경아교세포들이 조현병 병리에 어떤 역할을 하는지에 관한 연구가 집중되었다.4) 최근 들어 조현병에서 신경아교세포의 이상 소견에 대한 보고가 증가는 하고 있지만, 아직 신경아교세포가 조현병발병에 일차적 원인인지 이차적 현상인지에 대해서는 논란이있다.5)본 논문에서는 최근 조현병과 관련하여 관심이 증가하고있는 신경아교세포들의 구조적, 기능적, 병리적 소견들을 살펴보고, 이 세포들의 이상을 표적으로 하는 치료전략들을 살펴보고자 한다.

Abstract

In the past decade, structural, molecular, and functional changes in glial cells have become a major focus in the search for the neurobiological foundations of schizophrenia. Glial cells, consisting of oligodendrocytes, astrocytes, microglia, and nerve/glial antigen 2-positive cells, constitute a major cell population in the central nervous system. There is accumulating evidence of reduced numbers of oligodendrocytes and altered expression of myelin/oligodendrocyte-related genes that might explain the white matter abnormalities and altered inter- and intra-hemispheric connectivities that are characteristic signs of schizophrenia. Astrocytes play a key role in the synaptic metabolism of neurotransmitters ; thus, astrocyte dysfunction may contribute to certain aspects of altered neurotransmission in schizophrenia. Increased densities of microglial cells and aberrant expression of microglia-related surface markers in schizophrenia suggest that immunological/inflammatory factors are of considerable relevance to the pathophysiology of psychosis. This review describes current evidence for the multifaceted role of glial cells in schizophrenia and discusses efforts to develop glia-directed therapies for the treatment of the disease.

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