The Effects of Minocycline on Proliferation, Differentiation and Migration of Neural Stem/progenitor Cells

There are several attempts to enhance the capacities of neural stem/progenitor cells (NS/PCs) as a probable source of stem cell therapy for neurodegerative diseases. The evidence shows that minocycline has several non-antibacterial effects in neurodegenerative diseases. We aimed to investigate the effect of minocycline on proliferation, differentiation and migration of embryonic NS/PCs. NS/PCs extracted from ganglionic eminence of 13.5-day embryonic mice were cultured according to neurosphere protocol. After second passage they were exposed to different doses of minocycline for 7 days. The number and diameter of neurospheres were assessed to evaluate their proliferation. Migration was estimated based on the distances traveled by the cells. Because of the importance of NS/PCs behaviors in 3-dimentional environment, all assessments were done in 3-dimentional and 2-dimentional cultures. Moreover, the fate of NS/PCs to neuron or glial cells was studied. NS/PCs exposed to 1 μg/ml and 10 μg/ml of minocycline and those in untreated group traveled significantly longer distances compared to those treated with 50 μg/ml and 100 μg/ml of minocycline. In addition, higher doses of minocycline reduced the NS/PCs proliferation remarkably compared to control condition just in 2-D culture. However, the differentiation capacity of cells was not significantly affected by 1 and 10 μg/ml of minocycline. The behavior of NS/PCs depends on minocycline dose as well as the characteristics of environment.