Curcumin promotes neurogenesis of hippocampal dentate gyrus via Wnt/β-catenin signal pathway following cerebral ischemia in mice

Objectives: To investigate whether curcumin promotes hippocampal neurogenesis in the cerebral ischemia (CI) mice via Wnt/beta-catenin signaling pathway. Methods: Male C57BL/6 mice were randomly divided into groups: sham operation group (Sham), cerebral ischemic group (CI), curcumin treatment group (50, 100 mg/kg/d, i.p.) and curcumin (100 mg/kg/d) + DKK1 (a blocker of Wnt receptor, 200 ng/d, icv) group. CI was induced by bilateral common carotid arteries occlusion (BCCAO) for 20 min. The Morris water maze test was conducted to detect spatial learning and memory. Immunofluorescence staining was used to examine the proliferation and differentiation of immature neurons in the hippocampal dentate gyrus. The proteins involved in neurogenesis and Wnt signaling pathway were examined using Western blot assay. Results: Curcumin significantly alleviated cognitive deficits induced by CI. Curcumin dose-dependently increased the proliferation of neural stem cells and promoted the differentiation and maturation of newly generated neural cells into neurons. Curcumin also increased the expression of proteins involved in neurogenesis (including Ngn2, Pax6 and NeuroD 1) and the Wnt/beta-catenin signaling pathway. Moreover, the forenamed effects of curcumin were abolished by pretreatment with DKK1, a blocker of Wnt receptor. Conclusion: Curcumin promotes hippocampal neurogenesis by activating Wnt/beta-catenin signaling pathway to ameliorate cognitive deficits after acute CI.