Abstract—Rotenone is a pesticide that inhibits mitochondrial complex I activity, thus creating an environment of oxidative stress in the cell. Many studies have employed rotenone to generate an experimental animal model of Parkinson’s disease (PD) that mimics and elicits PD-like symptoms, such as motor and cognitive decline. Cytoprotective proteins including parkin and heat shock proteins (HSPs) play major roles in slowing PD progression. Moreover, evidence suggests that mitochondrial dysfunction and oxidative stress-dependent apoptotic pathways contribute to dopaminergic neuron degeneration In PD. Here, rats were chronically exposed to rotenone to confirm that it causes a debilitating phenotype and various behavioral defects. We also performed histopathological examinations of nigrostriatal, cortical and cerebellar regions of rotenone-treated brain to elucidate a plausible neurodegenerative mechanism. The results of silver, tyrosine hydroxylase (TH), park in, ubiquitin and caspase staining of brain tissue sections further validated our findings. The stress response is known to trigger HSP In response to pharmacological insult. These protective proteins help maintain cellular homeostasis and may be capable of rescuing cells from death. Therefore, we assessed the levels of different HSPs in the rotenone-treated animals. Collectively, our studies indicated the following findings in the striatum and substantia nigra following chronic rotenone exposure in an experimental PD model: (i) behavioral deficit that correlated with histopathological changes and down regulation of TH signaling, (ii) decreased levels of the cytoprotective proteins parkin, DJI and Hsp7O and robust expression of mitochondrial chaperone Hsp6O according to Western blot, (iii) increased immunoreactivity for caspase 9, caspase 3 and ubiquitin and decreased parkin immunoreactivity.
The presentation was neat and drew in valuable discussion among the listeners. The paper tried to emphasize that rotenone-induced Parkinson's disease model in rats, brings out the role of molecular mechanisms like that of HSPs (Heat shock proteins), which could be a potential target for therapeutic interventions.
Some interesting thoughts were:
- Why are rats naturally protected from Parkinson's disease? Or are they??
- What is the temporal scale of cellular & molecular changes associated with the disease development in this model?