This study demonstrates that STN lesions and dopamine agonists decreased the hyperactivity of the firing rate of SNpr neurons, and resulted in an increased firing rate of VL neurons in 6-OHDA lesioned rats. Concerning the firing pattern, the STN lesion was found to have a dramatic effect on SNpr neurons, but SKF38393 and Quinpirole did not. This result suggests that STN lesions and dopamine agonists may have different roles in the pathophysiology of PD.
The pathophysiological significance of bursting activity remains obscure, and the ability of dopamine agonist to regularize output nuclei firing patterns may explain why dopamine agonists lose efficacy as PD progress.
32
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40 국문요약
6-Hydroxydopamine에 의해 유도된 흰쥐 파킨슨병 모델에서 시상밑핵 손상과
도파민 수용체 작용물질의 효과
<지도교수 장 진 우>
연세대학교 대학원 의과학사업단
전 미 파
선조체의 도파민 수용체로 오는 도파민의 손실은 시상밑핵의 과도한 출 력을 유도하고 이것은 기저핵의 과도한 출력을 낳는다. 시상밑핵의 출력을 줄이는 것은 파킨슨병으로 오는 운동장애 증상을 회복시키기 때문에 연구 되어져 왔다. 시상밑핵의 손상은 그것의 과도한 출력을 줄일 수 있고 기저 핵에서 일어나는 운동조절시스템의 일시적인 장애를 정상화 시킬 수 있다.
또 다른 접근으로는 선조체에 있는 도파민 D1 수용체와 D2 수용체를 자극 하여 간접적인 시상밑핵의 출력을 감소시키는 것이있다. 이 연구에서 억제 성인 담창구를 거쳐 시상밑핵에서 나오는 출력을 감소시킨다고 생각되어 지 는 D1 수 용 체 작 용 물 질 인 S K F 3 8 3 9 3 과 D2 수 용 체 작 용 물 질 인 Quinpirole을 각각 선조체에 직접 주입하였다. 그런 후 기저핵의 출력을
41
보기위해 흑질그물부 (SNpr)와 복측외측의 시상 (VL)을 미세전극기록하 였다. 흑질그물부와 복측외측의 시상부위가 Kainic acid에 의한 시상밑핵 의 손상에 의해 어떻게 영향을 받는지 기록된 출력의 비율 (firing rate)과 형태 (firing pattern)에 따라 분석하였고, 출력의 형태는 규칙적인 형태와 (regular non bursting pattern) 불규칙한 형태 (bursting pattern) 로 분 리하여 분석하였다. 흰쥐 파킨슨모델 SKF38393는 흑질그물부의 출력을
42
은 파킨슨병의 병리생리학적 소견으로 시상밑핵에 의한 변화와 도파민 수 용체 작용물질에 의한 작용이 다른 경로로 이뤄진다는 것을 예측할 수 있
다 .
핵심되는 말: 6-OHDA, 파킨슨 병, 시상밑핵, 기저핵, kainic acid, 도파민
작용물질