Affiliation:
1. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2. Department of Neurology, Longevity District People’s Hospital of Chongqing, Chongqing 401220, China
Abstract
Activated microglia act as a double-edged sword for stroke. In the acute phase of stroke, activated microglia might deteriorate neurological function. Therefore, it is of great clinical transforming potential to explore drugs or methods that can inhibit abnormal activation of microglia in the acute phase of stroke to improve neurological function after stroke. Resveratrol has a potential effect of regulating microglial activation and anti-inflammation. However, the molecular mechanism of resveratrol-inhibiting microglial activation has not been fully clarified. Smoothened (Smo) belongs to the Hedgehog (Hh) signaling pathway. Smo activation is the critical step that transmits the Hh signal across the primary cilia to the cytoplasm. Moreover, activated Smo can improve neurological function via regulating oxidative stress, inflammation, apoptosis, neurogenesis, oligodendrogenesis, axonal remodeling, and so on. More studies have indicated that resveratrol can activate Smo. However, it is currently unknown whether resveratrol inhibits microglial activation via Smo. Therefore, in this study, N9 microglia in vitro and mice in vivo were used to investigate whether resveratrol inhibited microglial activation after oxygen-glucose deprivation/reoxygenation (OGD/R) or middle cerebral artery occlusion/reperfusion (MCAO/R) injury and improved functional outcome via triggering translocation of Smo in primary cilia. We definitively found that microglia had primary cilia; resveratrol partially inhibited activation and inflammation of microglia, improved functional outcome after OGD/R and MCAO/R injury, and triggered translocation of Smo to primary cilia. On the contrary, Smo antagonist cyclopamine canceled the above effects of resveratrol. The study suggested that Smo receptor might be a therapeutic target of resveratrol for contributing to inhibit microglial activation in the acute phase of stroke.
Funder
National Natural Science Foundation of China
Tibet Nature Science Foundation of Tibet
Postgraduate Research and Innovation Project of Chongqing
Reference54 articles.
1. Microglia in neurodegeneration;Hickman;Nat. Neurosci.,2018
2. Microglia and Monocyte-Derived Macrophages in Stroke;Kim;Neurotherapeutics,2016
3. The biphasic function of microglia in ischemic stroke;Ma;Prog. Neurobiol.,2017
4. Meng, T., Xiao, D., Muhammed, A., Deng, J., Chen, L., and He, J. (2021). Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules, 26.
5. Resveratrol and Alzheimer’s Disease: Mechanistic Insights;Ahmed;Mol. Neurobiol.,2016
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献