Effect Of Liver X Receptor Activation On Hippocampal Neurogenesis In Mice With Cerebral Ischemia

Objective:To investigate the effect of liver X receptor activation on hippocampal neurogenesis and cognitive function in cerebral ischemia reperfusion(CI)mice,and its mechanisms.Methods:A total of 96 C57BL/6 mice were randomly divided into four groups:sham group without cerebral ischemia and control(Vehicle group),TO901317(TO90 group),and GSK2033(GSK2033 group,GSK2033 is an antagonist of LXRs)with cerebral ischemia,24 mice in each group.The cerebral ischemia mice model was induced via the bilateral common carotid artery occlusion.Sham group without occlude the bilateral common carotid artery,only separated.Changes in cognitive functions such as spatial learning and memory in mice were measured by morris water maze test.Observation of pathological changes in hippocampal CA1 region by HE staining.Immunofluorescence was executed to detect hippocampus DCX+?BrdU+and BrdU+/NeuN+cells.Western blotting was used to detect the protein expression of hippocampus LXR??LXR??ABCA1?Wnt3a,?-catenin,Neuro D1.Results:TO90 significantly ameliorated spatial learning and memory deficits induced by ischemia.It enhanced neural stem cells proliferation demonstrated by BrdU immunostaining at day 14,consistent with DCX~+cells.BrdU~+/NeuN~+cells and the ratio of the double-labeling to total BrdU~+cells were also largely increased by TO90 at day 28.The LXRs target gene ABCA1 was significantly increased by TO90.The expression of Wnt3a,?-catenin,NeuroD1 level was totally increased at day 14 in TO90 group.The forenamed effects of LXR were significantly decreased by GSK2033.Conclusions:LXRs activation can improve CI mice cognitive function by promoting hippocampal neurogenesis,which might be through the activation of Wnt/?-catenin signaling pathway in the mice hippocampal.