童年期肥胖对实验性自身免疫性脑脊髓炎小鼠抑郁症状及海马小胶质细胞的影响OA
Effects of childhood obesity on depressive symptoms and hippocampal microglia in experimental autoimmune encephalomyelitis mice
目的 探讨童年期肥胖对实验性自身免疫性脑脊髓炎(EAE)小鼠抑郁症状及海马小胶质细胞的影响.方法 选择来自4只无特定病原体级C57BL/6J母鼠生产的24只子代小鼠,采用随机数字表法分为观察组和对照组,21 d龄断乳后开始独立饲喂,观察组饲以60％脂肪供能饲料,对照组饲以10％脂肪供能饲料,并在12周龄时诱导EAE模型.通过糖水偏好试验和强迫游泳试验评估抑郁症状.采用免疫荧光检测分析小胶质细胞体投影面积、分支指数以及诱导型一氧化氮合酶(iNOS)、巨噬细胞甘露糖受体(CD206)相对荧光强度.采用酶联免疫吸附试验测定海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的相对浓度.结果 观察组在第6、9和12周龄时的体重大于对照组,差异均有统计学意义(均P＜0.05).观察组糖水偏好率小于对照组,强迫游泳不动时间大于对照组,差异均有统计学意义(P＜0.05).观察组iNOS的相对荧光强度大于对照组,CD206的相对荧光强度小于对照组,差异有统计学意义(均P＜0.05).观察组海马组织中的TNF-α和IL-1β表达水平高于对照组,差异有统计学意义(均P＜0.05).结论 童年期肥胖会影响海马组织中小胶质细胞的功能和炎症反应,加重EAE小鼠的抑郁症状.
Objective To explore the effects of childhood obesity on depressive-like behaviors and hippocampal microglia in experimental autoimmune encephalomyelitis(EAE)mice.Methods Twenty-four offspring mice delivered by four specific pathogen-free C57BL/6J female mice were selected and divided into observation group and control group by random number table method.All mice were fed separately after weaning at 21 days of age.The observation group was fed with 60％fat-energy diet,while the control group was fed with 10％fat-energy diet,and the EAE model was established at the age of 12 weeks.Sucrose preference test and forced swimming test were performed to evaluate depressive-like behaviors.Immunofluorescence assay was used to detect and analyze the soma projection area,branching index of microglia,as well as the relative fluorescence intensity of inducible nitric oxide synthase(iNOS)and CD206.Enzyme-linked immunosorbent assay(ELISA)was adopted to determine the relative concentrations of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in hippocampal tissues.Results The body weight of the observation group at the age of 6,9 and 12 weeks was higher than that of the control group,with statistically significant differences(all P＜0.05).The sucrose preference rate of the observation group was lower than that of the control group,and the immobility time in forced swimming test was longer than that of the control group,with statistically significant differences(all P＜0.05).The relative fluorescence intensity of iNOS in the observation group was higher than that in the control group,while the relative fluorescence intensity of CD206 was lower than that in the control group,with statistically significant differences(all P＜0.05).The expression level of TNF-α and IL-1β in hippocampal tissues of the observation group were higher than those of the control group,with statistically significant differences(all P＜0.05).Conclusion Childhood obesity can affect the function and inflammatory response of hippocampal microglia,and aggravate depressive-like behaviors in EAE mice.
罗浩源;柴嘉擎;王赵伟
312000 绍兴文理学院医学院嵊州市人民医院神经内科绍兴市人民医院神经内科
多发性硬化肥胖小胶质细胞抑郁海马
Multiple sclerosisObesityMicrogliaDepressionHippocampus
《浙江医学》 2026 (10)
1016-1020,后插1,6
浙江省医坛新秀培养计划项目(YTXX202201)浙江省基础公益研究计划项目(LGD22H090016)绍兴市卫生健康科技计划项目(2022KY015)
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