慢性皮质酮注射对小鼠抑郁样行为及脑糖原水平的影响

目的:探讨慢性皮质酮注射对小鼠抑郁样行为以及脑糖原水平的影响。方法:将40只雄性C57BL/6N小鼠随机分为正常对照组与模型组,模型组小鼠连续4周给予皮质酮皮下注射,构建慢性应激抑郁障碍小鼠模型。采用强迫游泳实验和旷场实验验证慢性应激模型的建立;放免法测定小鼠血清中皮质酮(CORT)水平;采用蛋白免疫印迹法检测海马突触素(SYP)和脑源性神经营养因子(BDNF)的蛋白表达水平;采用荧光间接测定法检测海马组织的糖原以及糖原合酶和糖原磷酸化酶的水平。结果:与正常对照组相比,模型组强迫游泳静止不动时间延长(P0.01)、自主活动能力降低(P0.01),表明慢性皮质酮注射诱导小鼠产生抑郁样行为。抑郁小鼠的皮质酮明显升高(P0.01)。皮质酮注射降低海马SYP和BDNF的蛋白表达(P0.01),同时海马组织糖原含量减少(P0.05),糖原合酶的活性降低(P0.05),而糖原磷酸化酶活性增加(P0.05)。结论:慢性皮质酮注射引起的海马神经元损伤和诱导小鼠抑郁样行为,可能与皮质酮降低海马糖原水平有关。

Influence of chronic corticosterone injection on depression-like behavior and brain glycogen levels in mice

AIM: To study the effect of chronic corticosterone (CORT) injection on the depression-like behaviors and the brain glycogen level in mice. METHODS: Male C57BL/6N mice (n=40) were randomly divided into normal control group and model group. The mice in model group were subcutaneously consecutively injected with CORT for 4 weeks. The mouse model of chronic stress depression was constructed. The forced swim test and open field experiment were conducted to prove chronic stress model. The serum level of CORT in the mice was measured by radioimmunoassay. The protein levels of hippocampal synaptophysin (SYP) and brain-derived neurotrophic factor (BDNF) were detected by Western blot. Hippocampus glycogen, glycogen synthase and glycogen phosphorylase were determined by indirect fluorescence measurement. RESULTS: Compared with normal control group, the immobility time of the forced swim test in model group was significantly lengthened (P<0.01), and the ability of spontaneous activity was reduced (P<0.01), indicating that chronic CORT injection induced depression-like behaviors in mice. The CORT level increased significantly (P<0.01) in model group. CORT injection decreased the protein expression of hippocampal SYP and BDNF (P<0.01), reduced hippocampal glycogen level (P<0.05) and glycogen synthase activity (P<0.05), and increased glycogen phosphorylase activity (P<0.05). CONCLUSION: Chronic CORT injection causes hippocampal neuron damage and induces the depression-like behaviors of mice, which may be associated with decreasing hippocampal glycogen level by CORT.