期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 25, 期 1, 页码 9-20出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2003.09.013
关键词
-
资金
- NIDA NIH HHS [DA-10044] Funding Source: Medline
- NIMH NIH HHS [MH-40899] Funding Source: Medline
- Telethon [GGP02035] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [P01MH040899] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA010044] Funding Source: NIH RePORTER
An impaired complex II (succinate dehydrogenase, SD) striatal mitochondrial activity is one of the prominent metabolic alterations in Huntington's disease (HD), and intoxication with 3-nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II, mimics the motor abnormalities and the pathology of HD. We found that striatal spiny neurons responded to this toxin with an irreversible membrane depolarization/inward current, while cholinergic interneurons showed a hyperpolarization/outward current. Both these currents were sensitive to intracellular concentration of ATP. The 3-NP-induced depolarization was associated with an increased release of endogenous GABA, while acetylcholine levels were reduced. Moreover, 3-NP induced a higher depolarization in presymptomatic R6/2 HD transgenic mice compared to wild-type (WT) mice, showing an increased susceptibility to SD inhibition. Conversely, the hyperpolarization did not significantly differ from the one recorded in WT mice. The diverse membrane changes induced by SD inhibition may contribute to the cell-type-specific neuronal death in HD. (C) 2003 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据