Exosomes Extracted from Adipose Tissue Stem Cells Alleviate Rotenone-Induced Nigrostriatal Neuro-Degeneration, Glial Cell Activation, Synucleinopathy and Motor Incoordination via Modulation of Autophagy/MiRNA7/MiRNA21

Backgrounds: Mesenchymal stem cells-extracted Exosomes (Ex) have now been proposed as a novel approach for neurologic diseases. We aimed to explore the potential neuroprotective role of Ex extracted from adipose tissue stem cells in a Rotenone (Rot) Parkinsonian rat model.Methods: For this work, thirty-six rats were allocated into 3 groups: control, Rotenone (1.5 mg/kg/day intra-peritoneal injection) and Rot + Ex (single intra-venous injection of 800 mu g protein suspended in 1 mL phosphate buffered saline in the rat tail vein). Behavioral and motor assessment of the rats at the different study groups was evaluated using catalepsy test, rotarod test and open field test. The Enzyme-linked immunosorbent assay (ELISA) study included assessment of the Substantia Nigra Pars Com-pacta (SNPc) & striatum levels of catalase, Nuclear factor-erythroid 2-related factor 2 (Nrf2), caspase-3 and Tumor protein 53 (P53). An immunohistochemical study was performed for evaluating the expression of Tyrosine Hydroxylase (TH), alpha-synuclein, Ionized calcium-binding adapter molecule 1 (Iba-1), Microtubule-associated protein 1A/1B-light chain 3 (LC3), P62 and Glial fibrillary acidic protein (GFAP). The expression of Micro-RNA 7 and Micro-RNA 21 was also measured.Results: Ex significantly (p < 0.05) improved the Rot-induced deterioration in motor functions. Ex also modulated SNPc & stria-tum levels of the oxidative stress markers catalase and Nrf2 and reduced the apoptotic proteins caspase-3 and P53. Ex also up-regulated microRNA miRNA-7 and down-regulated miRNA-21 expression. They also ameliorated the Rot-induced histopatho-logical nigrostriatal degeneration, alleviated alpha-synuclein deposition and restored dopaminergic neurons in SNPc & striatum as seen by TH immunostaining. In addition, Ex also mitigated Rot-induced microglial & astrocytic activation and modulated the autophagy markers LC3 and P62.Conclusion: Ex treatment exhibited neuroprotective potential against Rotenone-induced nigrostriatal neurodegeneration and synucleinopathy, presumably through anti-apoptosis, autophagy modulation and amelioration of oxidative stress.