Effect of liver X receptor activation on hippocampal neural stem cell proliferation and cognitive function in global cerebral ischemia/reperfusion mice / 中国药理学通报

ABSTRACT

Aim To investigate the effect of liver X receptor (LXR) activation on the proliferation of hippocampal neural stem cells in global cerebral ischemia/reperfusion (I/R) mice,and its mechanisms.Methods A total of 75 C57BL/6 mice were randomly divided into three groups,namely the sham operation group,the cerebral I/R group and the cerebral I/R with TO901317 treatment (I/R + TO90) group.The I/R mouse model was induced via the bilateral common carotid artery occlusion.HE staining was used to detect the pathological changes in hippocampal CA1 region.Immunohistochemistry was executed to detect hippocampus DCX + cells.Immunofluorescence of BrdU was implemented to detect the proliferation neural stem cell.Morris water maze test was used to assess spatial learning and memory in mice.Western blot was used to detect the expression of hippocampus LXRα,LXRβ,ABCA1,p-ERK1/2,t-ERK1/2,p-CREB,t-CREB,BDNF.Results LXR activation improved cognitive recovery(P ＜0.01),and induced the proliferation of neural stem cells (P ＜ 0.01) in I/R mice.The expressions of hippocampal ABCA1,p-ERK1/2,p-CREB,BDNF in I/R + TO90 group mice also increased (P ＜ 0.01).Conclusions LXR activation can induce the proliferation of hippocampal neural stem cells and facilitate cognitive recovery following global cerebral I/R in mice,which may be related to the activation of hippocampal ERK1/2-CREB-BDNF pathway and then promoting endogenous neurogenesis in the hippocampus DG region of I/R mice.