慢性束缚应激致抑郁小鼠模型中内侧前额叶皮层与小脑髓鞘化的年龄差异化研究  

Age-dependent differences of medial prefrontal cortex and cerebellum myelination in the chronic restraint stress-induced depression mouse model

作　　者：钟富旺 易如岚 周亮 Zhong Fuwang;Yi Rulan;Zhou Liang(Key Laboratory of Anesthesia and Organ Protection of Ministry of Education(in Cultivation),Zunyi Medical University,Zunyi Guizhou 563006,China;Key Laboratory of Brain Science,Zunyi Medical University,Zunyi Guizhou 563006,China;Department of Anesthesiology,the Second Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563006,China)

机构地区：[1]遵义医科大学麻醉与器官保护教育部重点实验室(培育),贵州遵义563006 [2]遵义医科大学脑科学特色重点实验室,贵州遵义563006 [3]遵义医科大学第二附属医院麻醉科,贵州遵义563006

出　　处：《遵义医科大学学报》2025年第3期219-226,233,共9页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82460242)。

摘　　要：目的 探索慢性束缚应激致抑郁小鼠模型中不同脑区髓鞘化的年龄差异。方法 3月龄与出生后7 d雄性C57小鼠分别进行慢性束缚应激21 d建立成年与幼年抑郁小鼠模型,行为学检测抑郁样行为。利用免疫组织化学检测成年与幼年抑郁小鼠模型内侧前额叶皮层与小脑中髓鞘结构改变;蛋白质印迹法检测成年与幼年抑郁小鼠模型内侧前额叶皮层与小脑中髓鞘相关蛋白的表达。进一步应用蛋白质印迹与免疫荧光探索成年与幼年抑郁小鼠模型内侧前额叶皮层髓鞘化改变与抑郁样行为的可能关联。结果 行为学结果显示,成年与幼年慢性应激小鼠均表现出抑郁样行为,而幼年应激小鼠还表现出过度活动现象;免疫荧光染色结果显示,成年与幼年抑郁小鼠模型内侧前额叶皮层处MBP信号减弱,而幼年抑郁小鼠模型小脑处MBP信号增强;蛋白质印迹显示,成年与幼年抑郁小鼠模型内侧前额叶皮层中髓鞘相关蛋白表达降低,而幼年抑郁小鼠模型小脑中髓鞘相关蛋白表达增加;此外,成年与幼年抑郁小鼠模型内侧前额叶皮层中神经元与髓鞘相互作用的关键蛋白表达异常,神经元活性下降。结论 成年与幼年慢性应激致抑郁小鼠模型的内侧前额叶皮层存在髓鞘化缺陷,可能的机制是神经元与髓鞘的相互作用受损导致的神经元活性降低。Objective To investigate the age-dependent differences of central nervous system(CNS)myelination in the chronic restraint stress(CRS)-induced depression mouse model.Methods Male C57 mice of 3 month(adult)and postnatal 7(P7,juvenile)age were performed CRS for 21 days to generate the depression model.Behavior tests were performed to monitor the depression-like behaviors in the CRS mouse models at different ages.Immunohistochemistry(IHC)was used to examine the myelin structure changes in the medial prefrontal cortex(mPFC)and cerebellum(CB)of CRS mice at different ages.Western blotting(WB)was used to monitor the expression of myelin-related proteins in the mPFC and CB.Furthermore,WB and IHC were performed to reveal the possible mechanism under depression-related myelination dysfunction.Results Behavior tests showed that both adult and juvenile depression mice exhibited depression-like behaviors,meanwhile,the juvenile models showed hyperactivity.MBP staining showed decreased myelin structure in the mPFC of both adult and juvenile CRS mice,while the enhanced myelin structure was only observed in the CB of the juvenile CRS mice.WB revealed that CRS caused decreased expression level of myelin-associated proteins MBP and MOG in the mPFC of both adult and juvenile CRS mice,but increased MBP and MOG level in the CB of the juvenile CRS mice.Additionally,WB showed that the expression of Lingo-1 and MCT1,which are the key molecules to mediate to crosstalk between neuron and myelin,were disrupted in the mPFC of both adult and juvenile CRS mice,along with the decreased neural activity revealed by c-Fos staining.Conclusion Myelination defect exhibited in the mPFC of both adult and juvenile CRS mice,which may be attributed to the blunted neural activity caused by disrupted interaction between neuron and myelin in the CRS mPFC.

关 键 词：慢性束缚应激 抑郁 髓鞘化 年龄差异 内侧前额叶皮层 

分 类 号：R338.2[医药卫生—人体生理学]