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

Meurers BH(1), Zhu C, Fernagut PO, Richter F, Hsia YC, Fleming SM, Oh M,
Elashoff D, Dicarlo CD, Seaman RL, Chesselet MF.

Author information:
(1)Department of Neurology, UCLA, Los Angeles, CA 90095, USA.

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.

DOI: 10.1016/j.nbd.2008.10.001
PMCID: PMC3731054
PMID: 19013527 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus