Subthalamic Lesion Protects Nigral Dopaminergic Neurons from 6-Hydroxydopamine-induced Cytotoxicity in the Rat Model of Early Parkinson’s Disease

J Korean Neurol Assoc > Volume 18(5); 2000 > Article

Journal of the Korean Neurological Association 2000;18(5): 609-616.

흰쥐를 이용한 조기 파킨슨병 모델에서 도파민성 신경세포 변성에 대한 시상하핵 파괴의 보호 역할

이광수*, 김영인*·박성민 ·김범생 ·정성우 ·이상봉

가톨릭대학교 의과대학 신경과학교실,가톨릭대학교 의과학연구원 겸임연구원*

Subthalamic Lesion Protects Nigral Dopaminergic Neurons from 6-Hydroxydopamine-induced Cytotoxicity in the Rat Model of Early Parkinson’s Disease

Kwang-Soo Lee, M.D.*, Yeong-In Kim, M.D.*, Seong-Min Park, M.D., Beum-Saeng Kim, M.D., Sung-Woo Chung, M.D., Sang-Bong Lee, M.D.

Department of Neurology, College of Medicine, The Catholic University of Korea Catholic Research Institutes of Medical Science*, Seoul, Korea

Abstract

Background : Subthalamic nucleus (STN) activity increases in patients and animal models of Parkinson’s disease. It has been proposed that the STN may play a role in the progressive death of nigral dopamine (DA) neurons in PD. We studied the role of the excitatory afferents from the STN in the death of nigral DA neurons after a striatal 6-hydroxy-dopamine (6-OHDA) injection in a 6-OHDA-induced early Parkinson rat model. Methods : Nigral DA neurons were counted using of tyrosine hydroxylase immunolabeling. Sprague-Dawley rats were subjected to unilateral, ibotenic acid-induced destruction of the STN 3 weeks after producing the early Parkinson model by injecting an intrastriatal 6- OHDA (8.75 μg). Sham lesions of the STN were made by injecting phosphate-buffered saline. One week after STN ablation, lesions of nigrostriatal DA neurons were induced by repeated intrastriatal injections of 6-OHDA (8.75 μg). Results : Intrastriatal injections of 6-OHDA caused a progressive loss of nigral tyrosine hydroxylase-positive DA neu-rons in a dose dependent manner (3.5 μg, 8.75 μg, 17.5 μg). The dose of 8.75 μg of 6-OHDA was suitable for the early Parkinson model. Previous ablation of the STN significantly attenuated the loss of DA neurons in rats receiving 6- OHDA. Sham lesions of the STN did not affect DA neuron death induced by the toxin. Conclusions : The results indi ?cate that excitatory inputs from the STN may contribute to the 6-OHDA-induced death of nigral DA neurons in the early state of Parkinson’s disease. J Korean Neurol Assoc 18(5):609~616, 2000 Key Words : Subthalamic nucleus, Substantia nigra, Dopaminergic neuron, Neuroprotection, 6-Hydroxydopamine, Excitatory mechanism