Evaluation of the Effect of Liposomal L-Dopa and Exosomes Derived from SH-Sy5y Cells on the Survival of Dopaminergic Neurons by Regulating the Expression of Bdnf and Dat Genes

Abstract

Introduction: Parkinson's disease is a progressive neurodegenerative complication in which dopaminergic neurons located in substrantia nigra are gradually lost. Currently, the combined therapy strategies received more attentions as potential therapeutic approaches for Parkinson's disease. This study aimed to evaluate the potential effects of exosomes released from SH-Sy5y cells and liposomal L-dopa drug on Parkinson's rat models.

Methods: Twenty five male Wistar albino rats, in 5 groups, were included in this study. Parkinson's rat models were induced through microinjection of 6-OHDA (2.5 mg/mL) into the right substrantia nigra. The exosomes released from SH-Sy5y cell line were isolated and administrated alone or in combination with liposomal L-Dopa to the defined model groups. The effects of the treatments were evaluated by behavioral testing, histological studies and expression changes of bdnf and dat genes by real-time PCR.

Results: The rats in groups received the combined liposomal L-Dopa and exosome treatment and liposomal L-Dopa alone showed a significant improvement in their movement abilities. Also, in the models treated with both exosomes and liposomal L-Dopa drug, a significant increase in the expression level of Bdnf and Dat genes was observed, while the increase in expression observed in separate treatments was not statistically significant (P>0.05).

Conclusion: The results of the present study showed that the use of L-Dopa with exosomes of SH-Sy5y cells had positive synergistic effects on increasing the expression of Bdnf and Dat genes and induced differentiation of neuronal progenitor cells into dopaminergic neurons and thus increased their population and survival is in the area.