Adenosine A 2A receptor deficiency prevents p38MAPK activation and apoptosis of prefrontal cortex cells in mice with chronic hypoxic hypercapnia / 中华物理医学与康复杂志

ABSTRACT

Objective:To observe the effect of genetic inactivation of adenosine A 2A receptor on apoptosis in the prefrontal cortex and on the expression of phosphorylated p38 mitogen-active protein kinase (p38MAPK) in mice with chronic hypoxic hypercapnia. Methods:Sixteen male wild-type mice and 16 male mice in which the adenosine A 2A receptor gene had been knocked out were randomly divided into a 4 weeks group (including 4HH+ /+ and 4HH-/- subgroups) and a normal control group (including NC+ /+ and NC-/- subgroups). The 4HH+ /+ and 4HH-/- group mice were exposed to an atmosphere containing 9-11% O 2 and 5-6% CO 2 8 hours a day, 6 days a week for 4 weeks. The apoptosis index (AI) in their prefrontal cortices was then evaluated using terminal-deoxynucleoitide transferase mediated nick end labelling (TUNEL) staining. The expression of p38MAPK protein in the prefrontal cortices was measured using western blotting. Results:The average AI had increased significantly in the 4HH+ /+ and 4HH-/- groups compared with the controls, with significantly more apoptotic cells in the 4HH+ /+ group than in the 4HH-/- group. In the 4HH+ /+ and 4HH-/- groups the average expression of p38 protein in the prefrontal cortex was significantly higher than among their controls. Moreover, the average expression of p-p38MAPK protein in the prefrontal cortex of the 4HH-/- group was significantly lower than in the 4HH+ /+ group.Conclusion:Adenosine A 2A receptor knockout inhibits apoptosis in the prefrontal cortex and down-regulates the p38MAPK activation of mice after exposure to chronic hypoxic hypercapnia.