Synergistic Effect of Lovastatin and Selegiline on the Differentiation of Bone Marrow Stromal Cells Into Neuron-Like Cells

Abstract

Background: The effect of selegiline as an oxidase inhibitor on cell differentiation into neuron-like cells has been demonstrated by altering gene expression. Based on the results of studies on the role of statins in neurotrophin regulation, in this study, we examined the effect of lovastatin (HMG-CoA reductase inhibitor) on the differentiation of bone marrow mesenchymal cells (BMSCs) into neuron-like cells. Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) type B. Since dopamine in the human brain is metabolized primarily by MAO-B, selegiline increases dopamine levels in the central nervous system. In addition to inhibiting MAO-B, selegiline also inhibits the uptake of dopamine and norepinephrine into presynaptic nerves and increases dopamine turnover. Methods: Bone marrow mesenchymal cells were collected from 28-day-old rats and cultured under standard conditions on the medium. The experimental groups in this study were as follows: BMSCs (control); BMSCs induced with 20 µM selegiline for 24 hours (experiment 1); BMSCs induced with 6 µM lovastatin for 24 hours (experiment 2); BMSCs were induced with 20 µM selegiline for 24 hours and 6 µM lovastatin for the next 24 hours (experiment 3). Real-time RT-PCR was performed to determine the mRNA levels of the nestin and NF-68 genes. Results: Real-time RT-PCR results showed that nestin and NF-68 mRNA levels were significantly increased in the co-treatment group (experiment 3) compared to the other experimental groups (P < 0.05). Conclusions: Based on the increased expression of nestin and NF-68 genes, the presence of lovastatin has a synergistic effect on neuronal differentiation and optimization of stem cell therapeutic approaches.