Neuron-selective changes in RNA transcripts related to energy metabolism in toxic models of parkinsonism in rodents

NEUROBIOLOGY OF DISEASE

卷:38

Article

Greene, James G.^1,2  Dingledine, Raymond^1,2  Greenamyre, J. Timothy^3,4 

[1] Emory Univ, Sch Med, Dept Neurol & Pharmacol, Atlanta, GA USA

[2] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA USA

[3] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA

[4] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA USA

关键词: Parkinson's disease;    Mitochondria;    Gene expression;    Rotenone;    MPTP;    Dopamine;    Substantia nigra;    Ventral tegmental area;   

DOI  :  10.1016/j.nbd.2010.03.014

来源: Elsevier

【 摘 要 】

Dopamine (DA) neurons in the substantia nigra (SNDA neurons) are among the most severely affected in Parkinson's disease (PD). Mitochondrial complex I inhibition by rotenone or MPTP can induce SNDA neurodegeneration and recapitulate motor disability in rodents. We performed a transcriptional analysis of the midbrain response to complex I inhibition focused on selected metabolic transcripts using quantitative real-time RT-PCR in conjunction with laser-capture microdissection (LCM) of immunofluorescently targeted SNDA and ventral tegmental area (VIA) DA neurons. There were DA neuron-selective alterations in metabolic transcripts in response to generalized complex I inhibition dependent on the behavioral response of the animal, and vulnerable SNDA neurons were more dynamic in their metabolic transcriptional response than less vulnerable VTADA neurons. The metabolic transcriptional response of DA neurons may contribute significantly to the ultimate toxicity associated with mitochondrial inhibition, and better understanding of this response may provide insight into potential targets for neuroprotection in PD. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

Free