The Role of Autophagy in Rotenone-Induced Neurotoxicity in Mice

Abstract

Rotenone is widely used insecticide and pesticide. It is an environmental neurotoxin that induces accumulation of α-synuclein and deterioration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Autophagymediated self-digestion of cytoplasmic inclusions may be defensive against neurodegeneration caused by rotenone toxicity. This study designed to assess the autophagy role in rotenone-induced neurotoxic effects. Sixteen C57 black 6 male mice were divided into rotenone & control groups, each group contains 8 mice: the rotenone group; mice were administrated rotenone (3 mg/kg/day intraperitoneally). In the control group carboxymethyl cellulose 0.5% (a vehicle for rotenone) was given as 3mL/Kg/day intraperitoneal. Neuro-behavioural locomotor tests, histopathological and immuno-histochemical analysis of the brain dopaminergic neuronal cells and counting of microtubule Associated Protein Light Chain 3 (LC3) positive cells expression were investigated. Results showed that rotenone administration increases the total distance travelled, numbers of line crossing, average speed, maximum speed and rotations of the animal's body. However, it significantly decreases the efficient path and the total mobile and immobile episodes and induced severe degenerative changes in histo-pathological examination. Also, it decreased significantly the quantity of LC3 positive cells in the brain sections of exposed mice i.e. neurodegeneration and inhibition of autophagy in dopaminergic system. From this study it can be concluded that rotenone can induce neurotoxicity through inhibition of autophagy.

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“…However, the current study of Zhang et al [148] showed that due to its link with Parkinson's disease, the use of rotenone was banned in many developed countries. In agreement with this study, [149] described the neurotoxicity nature of rotenone on mice indicating that rotenone has a hazardous effect on animals.…”