Role of GluR2 in chronic neuroinflammation-induced cognitive dysfunction in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of glutamate receptor 2 (GluR2) in cognitive dysfunction induced by chronic neuroinflammation in mice.Methods:Sixty adult male C57BL/6 mice, aged 8-10 weeks, weighing 18-25 g, were divided into 4 groups ( n=15 each) using a random number table method: control + dimethyl sulfoxide (DMSO) group (group C+ DMSO), control + AMPA receptor selective non-competitive antagonist CFM-2 group (group C+ CFM-2), lipopolysaccharide (LPS)+ DMSO group and LPS + CFM-2 group.In C+ DMSO group and C+ CFM-2 group, normal saline 0.2 ml was intraperitoneally injected every day for 10 consecutive days, and 10% DMSO 0.165 ml and CFM-2 33 μmol/kg (diluted to 0.165 ml with 10% DMSO) were intraperitoneally injected, respectively, on the 10th day after injection of normal saline.In LPS + DMSO group and LPS + CFM-2 group, LPS 0.5 mg/kg (diluted to 0.2 ml with normal saline) was intraperitoneally injected every day for 10 consecutive days, and 10% DMSO 0.165 ml and CFM-2 33 μmol/kg (diluted to 0.165 ml with 10% DMSO) were intraperitoneally injected, respectively, after LPS injection on the 10th day.The Y-maze test was performed at 48 h after the end of administration, then the animals were sacrificed, and the hippocampal tissues were taken for determination of the expression of GluR2, ionized calcium binding adapter molecule 1 (Iba1), tumor necrosis factor-α (TNF-α) (by Western blot) and the number of microglia in hippocampal CA1 area (by immunofluorescence). Results:Compared with group C + DMSO, the percentage of spontaneous alternation was significantly decreased, the expression of GluR2, Iba1 and TNF-α in hippocampus was up-regulated, the number of microglia in hippocampal CA1 area was increased ( P<0.05), and no significant change was found in the parameters mentioned above in group LPS + DMSO ( P>0.05). Compared with group LPS + DMSO, the percentage of spontaneous alternation was significantly increased, the expression of GluR2, Iba1 and TNF-α in hippocampus was down-regulated, and the number of microglia in hippocampal CA1 area was decreased in group LPS+ CFM-2 ( P<0.05). Conclusions:GluR2 is involved in chronic neuroinflammation-induced cognitive dysfunction through activation of microglia in mice.