Striatal Dysregulation of Angpt2 and Circadian Gene Expression in a Rotenone Rat Model of Parkinson's Disease.

Al Saeedy DY, Hawkins E, Dozmorov MG, Tripathi O, Mahdiani S et al.

J Mol Neurosci 2026

UNLABELLED: Rotenone is a naturally-occurring isoflavone that is used as a pesticide. Rotenone is also administered to rats to induce nigrostriatal dopaminergic neuron loss in an established model of Parkinson’s Disease (PD). However, the molecular mechanisms linking rotenone action to the emergence of PD-like phenotypes are poorly understood. Here, we characterize rotenone-induced gene dysregulation in the striatum. Male Lewis rats at 12–14 months received rotenone injected at 3 mg/kg, i.p. once daily for nine days. Behavioral effects of rotenone were verified using the bar test for catalepsy. RNA sequencing was carried out on RNA extracted from the striatum of rats receiving the full course of Rotenone treatment and vehicle-treated controls. Illumina PE150 sequencing to 30 M clusters per sample revealed several hundred differentially expressed genes (DEGs) at FDR < 5%. These included Dopa decarboxylase ( SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12031-026-02506-z.

4 Figures Extracted

Fig. 1 PMC

Experimental timeline of rotenone treatment. Rats received either rotenone (3 mg/kg) or vehicle for 9 days. Rotenone caused severe rigidity in some su...

Fig. 2 PMC

( A ) Mean body weight after daily rotenone injections. Beginning day 5, daily i.p. rotenone elicited significant weight loss compared to the vehicle-...

Fig. 3 PMC

(A) Plot of sample loadings on the top two principal components extracted from the RNA-seq data. Overall the samples show heterogeneity but there is ...

Fig. 4 PMC

Bar plot of qPCR assays to validate rotenone-induced differential expression of genes in the striatum detected in RNA-seq. Plots show the relative qua...