Treatment with Minocycline Suppresses Microglia Activation and Reverses Neural Stem Cells Loss after Simulated Microgravity

Abstract

The present study aimed to investigate the effect of microglia on simulated microgravity-induced hippocampal neurogenesis reduction and the possible mechanism underlying. Adult rats were treated with tail suspension for different times and the changes of neural stem cells (NSCs) were examined by immunohistochemistry. Then, minocycline was used to inhibit the activation of microglia, and the numbers of microglia and NSCs were detected after microgravity. Additionally, liquid protein chip analysis was applied to detect proinflammatory factors in hippocampus in order to find out the cytokines responsible for microglia activation after microgravity. The results revealed that microgravity increased the numbers of Iba1⁺ cells and decreased the numbers of BrdU⁺ and DCX⁺ cells in hippocampus but did not affect the ratio of NeuN⁺/BrdU⁺ cells to the total number of BrdU⁺ cells. After treated with minocycline, activated microglia were suppressed and the reduction of NSCs induced by microgravity recovered. Besides, compared with the control, higher concentrations of INF-γ and TNF-α were detected in the rats treated with microgravity. Our study provides the first evidence that microglia-mediated inflammation plays an important part in microgravity-induced neurogenesis reduction in hippocampus, and INF-γ and TNF-α secreted by microglia might be the key factors in this process.