Liposomal Form of L-Dopa and SH-Sy5y Cell-Derived Exosomes Modulate the Tyrosine Hydroxylase/Dopamine Receptor D2 Signaling Pathway in Parkinson's Rat Models.

Abstract

Parkinson's disease is a progressive neurodegenerative disorder in which dopaminergic neurons located in the substantia nigra are gradually lost. Currently, combined treatment strategies are receiving increasing attention as potential therapeutic approaches for Parkinson's disease. This study aimed to evaluate the potential effects of exosomes released from SH-Sy5y cells and the liposomal form of L-dopa on Parkinson's rat models.Twenty-five male Wistar albino rats, in five groups, were included in this study. Parkinson's disease was induced through microinjection of 6-OHDA (2.5mg/mL) into the right substantia nigra. The exosomes released from the SH-Sy5y cell line were isolated and administered (0.2µg/5 µL) alone or in combination with the liposomal form of L-Dopa (80mg/kg) to the defined model groups. Behavioral tests and molecular assays were conducted to evaluate the expression levels of tyrosine hydroxylase (TH) and dopamine receptor D2 (DRD2).The rats in the groups receiving the combined liposomal form of L-Dopa and exosome treatment and the liposomal form of L-Dopa alone showed a significant improvement in their movement ability (p < 0.05). At molecular levels, these two groups also exhibited significant increases in Th (0.005 ± 0.001) and Drd2 (0.002 ± 0.0001) expression compared to controls (p < 0.05). The observed alterations of Th and Drd2 expression were not statistically significant in exosome- and L-Dopa-treated groups.The current study shows that exosome-derived neuronal cells and liposomal form of L-Dopa can protect different cells against pathological complications such as Parkinson's disease.