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6-OHDA로 유도된 파킨슨 증후군의 동물 모델에서 도파민성 신경세포의 손실과 미세아교세포 활성 사이의 관계

Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model

이지용|양영철|조병필|조원길|이진숙
대한체질인류학회|2013.03|해부·생물인류학 (Anatomy & Biological Anthropology)|제26권 제1호|pp. 13-23|DOI 10.11637/aba.2013.26.1.13

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MicrogliaDopaminergic neuron6-hydroxydopamine파킨슨증후군도파민성 신경세포미세아교세포Parkinsonian
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초록

본 연구는 6-OHDA로 유도된 파킨슨증후군 동물 모델에서 활성화된 미세아교세포의 형태학적 특징및 면역학적 표현형의 변화와 도파민성 신경세포와의 병리역학적 관계를 확인해 보고자 하였다. 오른쪽 안쪽앞뇌다발에 6-OHDA을 주입하여 흑색질 치밀부에 있는 도파민성 신경세포의 변성을 유도하였다. 동물모델을 6-OHDA 주입 후 1주, 2주, 4주 그리고 8주에 각각 희생시켰다. 활성화된 미세아교세포의 기능적 활성의 변화를확인하기 위하여 미세아교세포의 포식작용 표지자인 ED1과 쥐 활성미세아교세포 특이적 표지자인 OX6을 사용하여 면역조직화학법 염색을 수행하였다. 활성화된 미세아교세포는 6-OHDA 주입 후 1주에 흑색질 치밀부에있는 변성된 세포돌기 그리고 도파민성 신경세포의 세포체 등에 선택적으로 부착되어 있는 것을 확인할 수 있었고 이어서 흑색질 치밀부의 도파민성 신경세포와 신경섬유의 뚜렷한 손실을 나타내었다. 포식단계의 활성화된 미세아교세포는 6-OHDA 주입 후 2주에 가장 뚜렷하게 나타났고 시간이 지남에 따라 점진적으로 줄어 들었지만 6-OHDA 주입 후 8주까지 남아 있는 것을 확인하였다. 또한 이는 흑색질 치밀부에 있는 도파민성 신경세포수 계측의 결과와 일치함을 보였다. 이와 같은 결과는 미세아교세포의 활성은 도파민성 신경세포의 변성과정에 영향을 주어 도파민성 신경세포의 손실을 촉진하며 지속적으로 신경세포사를 이끈다는 것을 시사한다.

Abstract

This study assessed the dynamics of morphological and immunophenotypic properties of activated microglia in a 6-hydroxydopamine (6-OHDA) induced Parkinsonian animal model. Neurodegeneration in the substantia nigra pars compacta (SNc) was induced by unilateral injection of 6-OHDA into the medial forebrain bundle. Parkinsonian animal model were sacrificed at 1, 2, 4 and 8 weeks after 6-OHDA injection. Changes in the functional activity of activated microglia were identified using different monoclonal antibodies: OX6 for major histocompatibility complex (MHC) class II, ED1 for phagocytic activity. Phagocytic microglia, characterized by ED1- or OX6-immunoreactivity, appeared in the SNc at 1 week after 6-OHDA injection, activated microglia selectively adhered to degenerating axons, dendrites and dopaminergic neuron somas in the SNc. This was followed by significant loss of these fibers and nigral dopaminergic neurons. Activation of microglia into phagocytic stage was most pronounced at 2 week after 6-OHDA injection and gradually subsided, but phagocytic microglia persisted until 8 weeks after 6-OHDA injection. Taken together, our results indicate that activated microglia is lead to persistently neuron cell death and promotes loss of dopaminergic neuron by degeneration of the dopaminergic neurons.

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