Role of adenosine A1 receptors in hippocampal neurons in cognitive dysfunction caused by isoflurane anesthesia in aged mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of adenosine A1 receptors in hippocampal neurons in the cognitive dysfunction caused by isoflurane anesthesia in aged mice.Methods Sixteen male adenosine A1 receptor gene knockout homozygote mice (gene knockout mice) and 16 male wild-type mice,aged 18-22 months,weighing 27-32 g,were studied.Each type of mice was randomly divided into 2 groups (n=8 each) using a random number tablecontrol group (group C) and isoflurane anesthesia group (group Ⅰ).Mice inhaled 1.4％ isoflurane in 100％ O2 for 2 h in group Ⅰ,and 100％ O2 for 2 h in group C.All the mice underwent Morris water maze test at 24 h after isoflurane or O2 inhalation.After the test,the mice were sacrificed and the hippocampal tissues were harvested to determine the number of β-amyloid1-42 (Aβ1-42) plaques (using immunohistochemistry) and expression of phosphorylated tau (p-tau) protein,and 2B subunit-containing N-methyl-D-aspartate receptors (NR2B) (by Western blot analysis).Results Compared with group C of wild type mice,the escape latency was significantly prolonged,the number of Aβ1-42 plaques was enlarged,the expression of p-tau protein was up-regulated,and the expression of N R2B was down-regulated in group Ⅰ of wild type mice.Compared with group Ⅰ of wild type mice,the escape latency was significantly shortened,the number of Aβ1-42 plaques was decreased,the expression of p-tau protein was down-regulated,and the expression of NR2B was up-regulated in group Ⅰ of gene knockout mice.There was no significant difference in the parameters mentioned above between group Ⅰ and group C of gene knockout mice.Conclusion Adenosine A1 receptors in hippocampal neurons mediate isoflurane anesthesia-induced cognitive dysfunction in aged mice,and the mechanism may be related to promotion of deposition of Aβ,phosphorylation of tau protein and inhibition of activities of NR2B.