Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway
Li Sun, Ruili Han, Fei Guo, Hai Chen, Wen Wang, Zhiyang Chen, Wei Liu, Xude Sun, Changjun Gao
Abstract
We aimed to investigate the exact effect of IL-17 on regulating neural stem cells (NSCs) stemness and adult neurogenesis in ischemic cortex after stroke, how Astragaloside IV(As-IV) regulated IL-17 expression and the underlying mechanism. Photochemical brain ischemia model was established and IL-17 protein expression was observed at different time after stroke in WT mice. At 3 days after stroke, when IL-17 expression peaked, IL-17 knock out (KO) mice were used to observe cell proliferation and neurogenesis in ischemic cortex. Then, As-IV was administered intravenously to assess cell apoptosis, proliferation, neurogenesis, and cognitive deficits by immunochemistry staining, western blots, and animal behavior tests in WT mice. Furthermore, IL-17 KO mice and As-IV were used simultaneously to evaluate the mechanism of cell apoptosis and proliferation after stroke in vivo. Besides, in vitro, As-IV and recombinant mouse IL-17A was administered, respectively, into NSCs culture, and then their diameters, viable cell proliferation and pathway relevant protein was assessed. The results showed knocking out IL-17 contributed to regulating PI3K/Akt pathway, promoting NSCs proliferation, and neurogenesis after ischemic stroke. Moreover, As-IV treatment helped inhibit neural apoptosis, promote the neurogenesis and eventually relieve mice anxiety after stroke. Unsurprisingly, IL-17 protein expression could be downregulated by As-IV in vivo and in vitro and they exerted antagonistic effect on neurogenesis by regulating Akt/GSK-3β pathway, with significant regulation for apoptosis. In conclusion, IL-17 exerts negative effect on promoting NSCs proliferation, neurogenesis and cognitive deficits after ischemic stroke, which could be reversed by As-IV.