Role of CREB in pathogenesis of postoperative cognitive dysfunction in aged mice
Abstract：Objective To study the role of cyclic AMP response element binding protein (CREB)/ brain derived neurotrophic factor (BDNF) pathway in pathogenesis of POCD in aged mice.Methods Seventy-two aged male C57BL/6 mice were randomly divided into control group,isoflurane group,operation group,and isoflurane +operation group (18 in each group).After they received sham operation,1.8％ isoflurane inhalation for 1.5 h,abdominal operation under local anesthesia and abdominal operation under local anesthesia+1.8％ isoflurane inhalation for 1.5 h respectively,their cognitive function was assessed by fear conditioning behavioral test.Expressions of CREB,BDNF and p-CREB in hippocampus were detected by Western blot on days 1,3,7 after operation.Results Context and tone test showed the percentage of freezing time was lower in operation group than in other 3 groups on day 3 after operation.Context test showed the percentage of freezing time was lower in operation group than in other 3 groups on days 1 and 7 after operation.The ratio of p-CREB/CREB in hippocampus was lower in operation group than in other 3 groups on days 1 and 3 after operation.The expression level of BDNF was lower in operation group than in other 3 groups on days 3 and 7 after operation (P＜0.05,P＜0.01).Conclusion Abdominal operation can induce early postoperative cognitive impairment in aged mice while abdominal operation under isoflurane inhalation anesthesia can protect the cognitive function in aged mice.Inhibition of CREB/BDNF pathway is the mechanisms for POCD in aged mice.
Keywords：cyclic AMP response element-binding proteinbrain-derived neurotrophic factorcognition disordersisofluranesynapses
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 755-758 )