Variable effects of chronic subcutaneous administration of rotenone on striatal histology

The Journal of Comparative Neurology
Chunni ZhuMarie-Françoise Chesselet

Abstract

When infused in rats, rotenone, a mitochondrial complex I inhibitor, induces alterations that resemble the histological changes of Parkinson's disease, particularly degeneration of the nigrostriatal dopaminergic system. However, the specificity of rotenone effects has been challenged recently. We have re-examined the alterations caused by rotenone in the substantia nigra and the striatum of rats after infusion of rotenone (2 mg/kg per day s.c.) for 21 days. Three patterns of striatal tyrosine-hydroxylase immunoreactivity (TH-IR) were observed: 46% of animals showed no reduction, and 46% of animals showed diffuse reduction in TH-IR, whereas one animal presented a focal loss of TH-IR in the striatum. Confocal microscopy analysis showed that the vesicular monoamine transporter (VMAT2) was decreased in parallel with TH-IR, strongly suggesting a loss of striatal DA nerve terminals in animals with diffuse or central TH-IR loss. However, no significant loss of TH-IR neurons was observed in the substantia nigra. Analysis of NeuN and DARPP-32 immunoreactivity, and Nissl staining, in the striatum showed no striatal neuronal loss in animals with either preserved TH-IR or diffuse TH-IR reduction. However, in the animal with focal TH-IR los...Continue Reading

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