Curcumin Promotes Neurogenesis Via Wnt/?-catenin Singnal Pathway Following Cerebral Ischemia In Mice

Aim: To investigate the effect of curcumin on hippocampal neurogenesis after cerebral ischemia,and to explore the possible involved mechanisms.Methods: Male C57BL/6 mice were randomly divided into 5 groups(n=25): sham operation group(Sham),model group(Model),curcumin treatment groups(50,100mg/kg/d,ip,7 days)and curcumin(100 mg/kg/d)+ DKK1(200 ng/d,ivc)groups.The model of cerebral ischemia was established by clipping the bilateral common carotid arteries.HE staining was performed after ischemia 3 days.BrdU(50 mg/kg,ip,tid)was injected on day 6 and day 7 after ischemia.Immunofluorescence staining of BrdU positive cells and expression of neuronal precursor cell marker doublecortin(DCX)protein was performed on day 7 after surgery.On day 28 after surgery,immunofluorescence of BrdU/NeuN was used to detect the differentiation ability of neural stem cells(NSCs)and water maze test was used to detect the learning and memory ability of mice.On day 7 after ischemia,Western blot was used to analyze neurogenesis-associated protein: neurogenin 2(Ngn 2),the paired box gene 6(Pax6),and neuronal differentiation 1(NeuroD 1),and the expression of Wnt3 a,p-GSK3?/GSK3? and ?-catenin protein in the Wnt signaling pathway.Results: The ability of learning and memory in mice after cerebral ischemia was impaired(P<0.05),and the survival of alive neurons in hippocampal CA1 area was significantly reduced(P<0.05).On day 7 after ischemia,the number of BrdU-positive cells,the expression of DCX protein and BrdU/NeuN-positive cells were increased in model group.Compared with Sham group,the expression of Ngn2,Pax6,and NeuroD1 protein increased in model group(P<0.05).Meanwhile,Wnt3 a,p-GSK3?/GSK3? and ?-catenin protein expression also were significantly increased in model group(P<0.05).Curcumin significantly improved the ability of learning and memory in ischemic mice(P<0.05),and increased the number of alive neurons in hippocampal CA1 area(P<0.05).Curcumin dose-dependently increased the differentiation ability of NSCs and the neurogenesis-associated proteins expression(P <0.05),which was more than the increase in model group.Curcumin also dose-dependently increased Wnt/?-catenin signaling pathway protein expression(P<0.05).However,Dkk1,a blocker of Wnt receptor,attenuated these above effects of curcumin(P <0.05).Conclusion: Curcumin can promote the neurogenesis in the hippocampus following cerebral ischemia,and improve cognitive dysfunction after cerebral ischemia,which may be related to the activation of Wnt/?-catenin signaling pathway.