Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice

慢性皮质酮降低海马糖原水平及诱导小鼠抑郁样行为(英文)

Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system （CNS）, are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone （CORT） exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein （NF-L） and synaptophysin （SYP） levels, induced depression-like behavior in male mice, reduced hippocampal gly- cogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

目的:探讨慢性皮质酮(CORT)注射对脑糖原水平以及小鼠抑郁样行为的影响。创新点:首次发现长期注射皮质酮可减少海马糖原浓度,降低糖原合酶活性,但增加糖原磷酸化酶活性。方法:将40只雄性C57BL/6N小鼠随机分为正常对照组与模型组。对模型组小鼠进行连续四周的CORT皮下注射,构建慢性应激抑郁障碍小鼠模型。采用强迫游泳和悬尾实验,验证慢性应激模型的建立;采用放免法,测定小鼠血清中CORT水平;采用蛋白免疫印迹法,检测海马神经微丝轻链(NF-L)和突触囊泡蛋白(SYP)的表达水平;采用酶法,检测海马组织的糖原浓度以及糖原合成酶和糖原磷酸化酶的活性。结论:慢性CORT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CORT降低海马糖原水平有关。