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| Effect of acute stress on AMPA receptors trafficking and fear memory in mice |
| CHEN Yuanhao1 ZHOU Mengsheng1 YIN Xiaoyu1 HE Yi1 WANG Wei2 HAO Jingru1 HAN Yuan1 GAO Can1 |
1.Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Jiangsu Province, Xuzhou 221004, China;
2.Department of Neurology, the First People′s Hospital of Huainan, Anhui Province, Huainan 232007, China |
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Abstract Objective To investigate the effect of acute restraint stress on AMPA receptors trafficking and fear memory in mice and its mechanism. Methods Sixty-four male C57BL/6 mice were divided into control group, Propranolol group, restraint stress group, combined group (restraint stress + Propranolol), according to random number table method, with 16 mice in each group. In the propranolol group and combined group, 10 mg/kg Propranolol solution was administered intragastrically, at the same time, the control group and the restraintstress group were intragastrically administered with an equal volume of normal saline, and the administration volume were 20 mL/kg. After 30 minutes of administration, the restraint stress group and combined group were restrained with 50 mL EP tube for 30 minutes. The fear memory of mice was evaluated by fear conditioning test. The expression of GluA1 in hippocampus, the level of serine phosphorylation at the 831th (pS-831) and the 845th (pS-845) of GluA1, the expression of calcium/calmodulin dependent protein kinase Ⅱ (CaMKⅡ) and its phosphorylation (p-CaMKⅡ) level, and the expression of GluA1 in the hippocampus cell membrane were measured by Western blot. Results Compared with the control group, the context-dependent and tone-dependent freezing time in the restraint stress group increased (P < 0.05), the expression of pS-831, pS-845 and p-CaMKⅡ in hippocampus increasd (P < 0.05), and the expression of GluA1 in cell membrane increased (P < 0.05), while the expression of GluA1 and CaMKⅡ in total protein had no significant difference (P > 0.05). Compared with the restraint stress group, the context-dependent and tone-dependent freezing time in the combined group decreased (P < 0.05), the expression of pS831, pS845 and p-CaMKⅡ in hippocampus decreased (P < 0.05), and the expression of GluA1 in cell membrane decreased (P < 0.05), while the expression of GluA1 and CaMK Ⅱ in total protein had no significant difference (P > 0.05). Conclusion Acute restraint stress can promote the formation of fear memory in mice, which may be related to the regulation of GluA1 subunit phosphorylation and the increased trafficking of AMPA receptors. Moreover, β-adrenergic receptors (β-ARs) may be one of the important targets for restraint stress-induced fear memory.
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