RGD Reference Report - Rotenone-induced parkinsonism elicits behavioral impairments and differential expression of parkin, heat shock proteins and caspases in the rat. - Rat Genome Database

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Rotenone-induced parkinsonism elicits behavioral impairments and differential expression of parkin, heat shock proteins and caspases in the rat.

Authors: Sonia Angeline, M  Chaterjee, P  Anand, K  Ambasta, R K  Kumar, P 
Citation: Sonia Angeline M, etal., Neuroscience. 2012 Sep 18;220:291-301. doi: 10.1016/j.neuroscience.2012.06.021. Epub 2012 Jun 16.
RGD ID: 13463458
Pubmed: PMID:22710069   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2012.06.021   (Journal Full-text)

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), parkin, 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, DJ1 and Hsp70 and robust expression of mitochondrial chaperone Hsp60 according to Western blot, (iii) increased immunoreactivity for caspase 9, caspase 3 and ubiquitin and decreased parkin immunoreactivity.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PARK7HumanParkinsonism  ISOPark7 (Rattus norvegicus)protein:decreased expression:brainRGD 
Park7RatParkinsonism  IEP protein:decreased expression:brainRGD 
Park7MouseParkinsonism  ISOPark7 (Rattus norvegicus)protein:decreased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Park7  (Parkinsonism associated deglycase)

Genes (Mus musculus)
Park7  (Parkinson disease (autosomal recessive, early onset) 7)

Genes (Homo sapiens)
PARK7  (Parkinsonism associated deglycase)

Additional Information