Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and α-synuclein aggregation

被引:542
作者
Sherer, TB [1 ]
Kim, JH
Betarbet, R
Greenamyre, JT
机构
[1] Emory Univ, Dept Neurol, Ctr Neurodegenerat Dis, Atlanta, GA 30032 USA
[2] Chosun Univ, Coll Med, Dept Neurol, Kwangju, South Korea
关键词
mitochondria; Parkinson's disease; oxidative stress; complex I; pesticides;
D O I
10.1006/exnr.2002.8072
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous studies demonstrated that chronic systemic exposure to the pesticide and mitochondrial toxin rotenone through jugular vein cannulation reproduced many features of Parkinson's disease (PD) in rats, including nigrostriatal dopaminergic degeneration and formation of alpha-synuclein-positive cytoplasmic inclusions in nigral neurons (R. Betarbet et aL, 2000, Nat Neurosci. 3, 1301-1306). Although novel and conceptually important, the rotenone model of PD suffered from being extremely labor-intensive. The current paper demonstrates that these same features of PD can be reproduced by chronic, systemic exposure to rotenone following implantation of subcutaneous osmotic pumps. Chronic subcutaneous exposure to low doses of rotenone (2.0-3.0 mg/kg/day) caused highly selective nigrostriatal dopaminergic lesions. Striatal neurons containing DARPP-32 (dopamine and cAMP-regulated phosphoprotein) remained intact with normal morphology, and NeuN staining revealed normal neuronal nuclear morphology. Neurons of the globus pallidus and subthalamic nucleus were spared. Subcutaneous rotenone exposure caused alpha-synuclein-positive cytoplasmic aggregates in nigral neurons. This new protocol for chronic rotenone administration is a substantial improvement in terms of simplicity and throughput. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:9 / 16
页数:8
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