Possible role of lncRNAs in amelioration symptoms in an animal model of Parkinson’s disease following transplantation of dopaminergic cells derived from stem cells

Abstract

Abstract Background Long non-coding RNAs (lncRNAs) are important biomarkers for the pathogenesis of Parkinson's disease (PD) discovery and treatment approaches. Since dopaminergic cell transplantation is a promising clinical method to treat PD, this study investigated the effect of dopaminergic cell therapy on the expression of some lncRNAs and genes related to PD in the brains of rat models. Methods Twenty-eight rats were randomly assigned to four experimental groups. The animals injected with the saline solution were considered as control (Sal group). In the Par group, the PD rat model was developed by injecting 6-hydroxydopamine into the right striatum (ST). The ST of the animals was then transplanted by undifferentiated P19 stem cells (Par-E group), and/or P19-derived dopaminergic cells (Par-N group). The effects of cell transplantation were evaluated using behavioral tests (cylinder, open field, and rotarod tests), and histological methods (H&E, Nissl staining, and immunohistochemistry). Moreover, the expression of lncRNAs MALAT1, MEG3, and SNHG1 genes, as well as specific neuronal (synaptophysin, SYP) and dopaminergic (tyrosine hydroxylase, TH) markers was measured by qRT-PCR. Results Behavioral tests and histopathological evaluations showed that cell transplantation could partially compensate for dopaminergic cell degeneration in ST and substantia nigra (SN) of PD rats. The expression of MALAT1, SNHG1, and MEG3 was decreased in the ST of the Par group, while MEG3 and SNHG1gene expression was increased in PBMC compared to the Sal group. In PBMC of the Par-N group, all three lncRNAs showed a reduction in their expression. However, in ST tissue the expression of MALAT1 and SNHG1 was increased, while MEG3 gene expression was decreased compared to the Sal group. Conclusions Our data suggest that variations in the expression of lncRNAs genes may be considered as a marker for the possible incidence of PD.