Ischemic stroke is a major cause of mortality and disability. Subventricular zone (SVZ) neurogenesis following an ischemic stroke may be beneficial for improving the outcomes. Environmental enrichment (EE) has been reported to increase neurogenesis following stroke. Growth arrest and DNA-damage-inducible protein 45 β (Gadd45b) is a crucial gene for activity-correlated neurogenesis in the adult hippocampus of mice. This study examined whether Gadd45b inhibition affects adult SVZ neurogenesis after an ischemic injury and explored the role of Gadd45b in EE-induced SVZ neurogenesis in adult male Sprague Dawley rats following middle cerebral artery occlusion (MCAO). Gadd45b expression was silenced by a lentivirus with RNA interference (RNAi). The 5-ethynyl-2-deoxyuridine (EdU) staining test was performed to detect cell proliferation. Gadd45b-RNAi after MCAO decreased SVZ proliferation and differentiation in the infarction boundary following ischemic injury, accompanied by the depressed expression of the brain-derived neurotrophic factor (BDNF). Treatment with EE following ischemic stroke upregulated Gadd45b and BDNF expressions and increased neurogenesis in the SVZ. Inhibition of Gadd45b markedly ameliorated the increased neurogenesis induced by EE. These data indicated that Gadd45b is related to SVZ neurogenesis following ischemic stroke, and Gadd45b mediates EE-induced neurogenesis via BDNF in the SVZ of rats following an ischemia stroke. These results implicate that Gadd45b can be a potential therapeutic target to enhance adult neurogenesis following cerebral ischemia.
Keywords: BDNF; Environmental enrichment; Growth arrest and DNA-damage-inducible protein 45 β; MCAO; Neurogenesis.
Copyright © 2020. Published by Elsevier B.V.