Adiponectin promotes neurogenesis after transient cerebral ischemia through STAT3 mediated BDNF upregulation in astrocytes

作者：Liang Yu, Jiajia wang, Ying Xia, Wugang Hou, Xi Yao, Yaru Guo, Jin Wang, Haidong Wei, Shiquan Wang · 发表于：Research Square · 年份：2022 · DOI：10.21203/rs.3.rs-1576637/v1 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Neurogenesis and neuroplasticity mechanisms、Nerve injury and regeneration

Abstract Newborn neurons from the subventricular zone (SVZ) are essential to functional recovery following ischemic stroke. However, most of these newly generated neurons die quickly and fail to form functional connections with surrounding neurons. Thus, methods to promote neurogenesis and the survival of newborn neurons are of significance to post-stroke recovery. Adiponectin could increase neurogenesis in the dentate gyrus of hippocampus in neurodegenerative diseases. Therefore, we wonder whether adiponectin could also promote neurogenesis in SVZ and improve functional recovery after ischemic stroke. In addition, the critical role of astrocyte-derived BDNF in promotion of the neurogenesis should be verified. Here, we adopted the middle cerebral artery occlusion model of mice, and started the adiponectin treatment on day 3 of reperfusion. Neurogenesis and brain atrophy were analyzed by morphological methods, and neurological function was assessed by the adhesive removal test and the forepaw grip strength. The levels of BDNF and p-STAT3 were detected by western blotting. The adeno associated virus-encoded BDNF shRNA with GFAP promoter and a STAT3 inhibitor Stattic were used. We found that adiponectin improved neurological recovery, reduced brain atrophy, and increased both the doublecortin-positive cells and NeuN/BrdU double-positive cells. Mechanically, adiponectin increased the protein levels of p-STAT3 and BDNF in astrocytes, while silence of BDNF diminished the adiponecti...