Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo.

Article Details

Citation
Copy to clipboard

Meurers BH, Zhu C, Fernagut PO, Richter F, Hsia YC, Fleming SM, Oh M, Elashoff D, Dicarlo CD, Seaman RL, Chesselet MF

Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo.

Neurobiol Dis. 2009 Feb;33(2):182-92. doi: 10.1016/j.nbd.2008.10.001. Epub 2008 Oct 26.

PubMed ID
19013527 [ View in PubMed
]
Abstract

Mitochondrial complex I inhibition has been implicated in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease. However, the mechanisms and pathways that determine the cellular fate of DA neurons downstream of the mitochondrial dysfunction have not been fully identified. We conducted cell-type specific gene array experiments with nigral DA neurons from rats treated with the complex I inhibitor, rotenone, at a dose that does not induce cell death. The genome wide screen identified transcriptional changes in multiple cell death related pathways that are indicative of a simultaneous activation of both degenerative and protective mechanisms. Quantitative PCR analyses of a subset of these genes in different neuronal populations of the basal ganglia revealed that some of the changes are specific for DA neurons, suggesting that these neurons are highly sensitive to rotenone. Our data provide insight into potentially defensive strategies of DA neurons against disease relevant insults.

DrugBank Data that Cites this Article

Drugs