Role of hippocampal p75 neurotrophin receptor in postoperative cognitive dysfunction of aged mice / 中风与神经疾病杂志

ABSTRACT

@#Objective　To investigate the role of the p75 neurotrophic receptor (p75 NTR) in the cognitive impairment induced by laparotomy surgery of aged mice,and to explore the possible mechanism.Methods　Thirty eighteen-month-old male mice were equally randomized into three groups (n=10):control group,surgery group,surgery+TAT group.Open field test was performed 5 days after the surgery to record the exploration distance and the time in the center.Fear-conditioned training was performed 6 days after the surgery,and fear-conditioned test was performed 7 days after the surgery to record the freezing time.The hippocampus was harvested immediately after the behavioral test.Western blot was applied to detect the levels of p75NTR,BDNF,PSD95,TrkB and pCREB in the hippocampus,immunofluorescence was applied to detect the number of caspase-3 positive cells in the hippocampus,and Golgi staining was applied to observe the changes of dendritic spines in hippocampal CA-1 region.Results　In the open field test,the total distance and the time in the center had no significant difference among the three groups (P>0.05).In the fear conditioning test,compared with control group,the percentage of the contextual conditional freezing time decreased significantly in surgery group (P<0.05),and the expressions of BDNF，PSD95，TrkB and pCREB and the number of dendritic spines in CA-1 were significantly decreased (P<0.05),the expression of p75NTR and the number of caspase-3 positive cells were increased significantly in the surgery group (P<0.05).Compared with the surgery group,the percentage of the contextual conditional freezing time increased significantly in surgery+TAT group,and the expressions of BDNF,PSD95,TrkB,and pCREB and the number of dendritic spines in CA-1 were significantly increased,the number of caspase-3 positive cells were decreased significantly in the surgery+TAT group (P<0.05).Conclusion　Hippocampal p75 NTR plays a key role in the pathophysiology of POCD.