Selegiline induces adipose tissue-derived stem cells into neuron-like cells through MAPK signalingpathway

Introduction: Adipose-derived stem cells (ADSCs) are one of the most well-known and accessible sources of stem cells that can be used for the treatment of neurodegenerative diseases. On the other hand, previous studies have suggested that selegiline, as an irreversible inhibitor of monoamine oxidase, affects stem cells’ differentiation into neurons. This study was conducted to investigate the involvement in phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in ADSCs differentiation to neuron-like cells using selegiline as inducer. Methods: ADSCs were isolated from male rats, cultured in DMEM and then treated with selegiline (10-7 M) for 24h. Real-time PCR for nestin and neurofilament-68 (NF-68) was performed from the negative control (ADSCs at the 3rd passage), positive control (ADSCs were treated with 10-7 M selegeline for 24h, PI3AKT inhibitor (ADSCs were pretreated with treated with 10μM LY294002 for 3h, then10-7 M selegeline for the next 24h, and MAPK inhibitor (ADSCs were pretreated with treated with 10μM PD98059 for 3h, then10-7 M selegeline for the next 24h). Results: Nestin and NF-68 genes have been over-expressed in the selegiline-treated ADSCs. The PD98059 and LY294002 significantly down-regulated the selegiline-induced over-expression of nestin and NF-68; however, PI3K inhibition did not return the genes expression to control level. ADSCs were immunoreactivefor nestin and NF-68 about 98% and 95% respectively. Conclusion: According to the results, selegilinecan induce the gene expression of neural stem cell biomarkers in ADSCs through MAPK pathway activating and so differentiating them into neuron-like cells.