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

Authors
L Yu, Y Xia, W Hou et al

Lab
Fourth Military Medical University, Xi'an, China

Journal
Research Square

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 adiponectin-induced neurogenesis and functional recovery. Moreover, inhibition of STAT3 not only reversed the increase of BDNF but also the neurogenesis and functional recovery. Collectively, we conclude that adiponectin enhances neurogenesis and functional recovery after ischemic stroke via STAT3/BDNF pathway in astrocytes.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)