Ameliorative Potential of Mesenchymal Stem Cells-derived Exosomes on the Cerebellar Cortex in a Rat Model of Parkinson's Disease: Targeting HOTAIR/miRNA-221 Signaling Axis: A Histological, Immunohistochemical, and Biochemical Study

Among neurodegenerative diseases, Parkinson's disease (PD) is the second most common disorder. It is marked by the degeneration of dopaminergic neurons and depletion of dopamine. The mesenchymal stem cells (MSCs)-derived exosomes hold a promise for addressing neurodegeneration-associated neurological disorders owing to their distinctive immunomodulatory and regenerative properties. The investigation explored the therapeutic potential of MSCs-derived exosomes to mitigate the pathological changes in the cerebellar cortex in a rat model of PD. Thirty rats were divided into control, PD, and PD-BM-MSCs-derived exosomes groups. For 5 weeks, rodents were administered a subcutaneous injection of 2 mg/kg/day of rotenone to induce a PD model. The PD group exhibited a substantial increase in relative cerebellar mRNA HOTAIR, BAX, and caspase 3 gene expression, along with a concomitant decrease in relative cerebellar miRNA-221 gene expression. Light and transmission electron microscopy also depicted marked degenerative changes in the cerebellar cortex. The immune expression of glial fibrillary acidic protein and ionized calcium-binding adaptor molecule-1 markedly increased, while synaptophysin expression markedly decreased. Interestingly, all changes showed a significant regression following treatment with exosomes derived from BM-MSCs. In conclusion, BM-MSCs-derived exosomes may be a promising PD intervention strategy.