چكيده لاتين
Background: Long non-coding RNAs (lncRNAs) are important biomarkers for the pathogenesis of Parkinsonʹs disease (PD). Since dopaminergic cell transplantation is a promising clinical method to treat PD, this study aims to investigate 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 Wistar rats were randomly assigned to four experimental groups. Sal (Control: Rats injected with isotonic saline solution). Par (PD model rat: 6-OHDA-lesioned animals); Par-E (PD rats under cell therapy: an embryonic stem cell line, P19 transfected with pCMV3-GFPSpark vector and injected into animals). Par-N (PD rats under cell therapy: P19 cells transfected with pCMV3-C-NR4A2-GFPSpark vector and injected into animals). 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 the ST of the Par-N group, the expression of MALAT1 and SNHG1 was increased, while MEG3 gene expression was decreased compared to the Sal group. On the other hand, TH expression was reduced following lesioning, but cell therapy was able to significantly increase it so that it was not significantly different from the Sal group. Finally, synaptophysin expression was reduced in the Parkinsonʹs group, and cell transplantation was unable to increase it compared to the Parkinsonʹs group.
Conclusions: Dopaminergic cell transplantation can alter lncRNA expression and partially ameliorate Parkinsonʹs disease symptoms in rats.
