Wip1 knockout inhibits neurogenesis by affecting the Wnt/β-catenin signaling pathway in focal cerebral ischemia in mice

Neurogenesis correlates closely with the recovery of neural function after brain ischemia but the critical proteins and signaling pathways involved remain unclear. The phosphatase WIP1 has been shown to regulate neurogenesis in models of aging. However, it is not known if WIP1 affects neurogenesis and functional recovery after brain ischemia. To explore these questions, we performed permanent middle cerebral artery occlusion (MCAO) in mice and performed BrdU labeling, neurobehavioral testing, western blotting, and immunofluorescence staining. We found that ischemia induced WIP1 expression in the area bordering the injury. Compared to wild-type mice, the knockout of the Wip1 gene inhibited neurological functional recovery, reduced the expression of doublecortin, and inactivated the Wnt/β-Catenin signaling pathway in cerebral ischemia in mice. Pharmacological activation of the Wnt/β-Catenin signaling pathway compensated for the Wip1 knockout-induced deficit in neuroblast formation in animals with MCAO. These findings indicate that WIP1 is essential for neurogenesis after brain injury by activating the Wnt/β-Catenin signaling pathway. •Wip1 knockout inhibited neurogenesis after brain ischemia in mice.•Wip1 knockout inactivated the Wnt/β-Catenin signaling pathway in ischemic brain in mice.•SB216763 rescued neurogenesis in Wip1 knockout mice after stroke.