Rotenone

Rotenone is an inhibitor of mitochondrial electron transport at NADH:ubiquinone oxidoreductase, and is used to induce a Parkinson-like syndrome as an experimental model in rats.

Mitogen Activated Protein Kinase (MAPK), Toll-like receptor, Wnt, and Ras signaling pathways are intensively involved in the effect of rotenone on the ENS^[2]. Rotenone-induced cell death is reduced by MCE treatment as measured by decline in the levels of pro-apoptotic proteins. Moreover, MCE treatment significantly augments the levels of anti-apoptotic Bcl2 and blocks the release of cytochrome c, thereby alleviating the rotenone-induced dopaminergic neuronal loss, as evidenced by tyrosine hydroxylase (TH) immunostaining in the striatum^[3].

Rotenone causes a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine are observed in the cerebellum of rat model of PD^[1]. Rotenone (1.5, 2, or 2.5 mg/kg) causes a dose-dependent increase in α-synuclein in the substantia nigra. Furthermore, at 2 and 2.5 mg/kg, rotenone causes a significant decrease in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, and dopamine in the striatum in rats^[4].

• [1]. Khadrawy YA, et al. Cerebellar neurochemical and histopathological changes in rat model of Parkinson's disease induced by intrastriatal injection of rotenone. Gen Physiol Biophys. 2016 Nov 30.

  [2]. Guan Q, et al. RNA-Seq Expression Analysis of Enteric Neuron Cells with Rotenone Treatment and Prediction of Regulated Pathways. Neurochem Res. 2016 Nov 30.

  [3]. Kishore Kumar SN, et al. Morinda citrifolia mitigates rotenone-induced striatal neuronal loss in male Sprague-Dawley rats by preventing mitochondrial pathway of intrinsic apoptosis. Redox Rep. 2016 Nov 24:1-12.

  [4]. Zhang ZN, et al. Subcutaneous rotenone rat model of Parkinson's disease: dose exploration study. Brain Res. 2016 Nov 19. pii: S0006-8993(16)30776-4.