The Role of Autophagy in Rotenone-Induced Neurotoxicity in Mice | ||||
Mansoura Journal of Forensic Medicine and Clinical Toxicology | ||||
Article 2, Volume 28, Issue 1, January 2020, Page 15-23 PDF (1.42 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/mjfmct.2019.17909.1001 | ||||
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Authors | ||||
Eman Abdelrazik 1; Amal El-Bakary 2; Samera Shaaban2; Mohamed Salama3; Amany Hassan4; Sara El-desouky5; Adel EL-Mansoury2 | ||||
1Forensic Medicine and Clinical Toxicology Department ,Faculty of Medicine Mansoura University, Egypt | ||||
2Forensic Medicine and Clinical Toxicology Department, Mansoura Faculty of Medicine, Egypt | ||||
3Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Egypt/ Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt. | ||||
4Pathology Department,Mansoura University, Mansoura, Egypt. | ||||
5Veterinarian in Medical Experimental Research Center (MERC), Mansoura University, Mansoura, Egypt | ||||
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). Autophagy-mediated 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, histo-pathological 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. | ||||
Keywords | ||||
Neurotoxicity; Rotenone; Mice; autophagy | ||||
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