小胶质细胞M1型极化诱发小鼠焦虑样行为及其对前额叶神经元树突棘密度的影响

发布时间：2018-06-03 14:31

本文选题：小胶质细胞极化 + 焦虑样行为　；参考：《神经解剖学杂志》2017年04期

【摘要】：目的:焦虑样行为与脑内小胶质细胞M1型极化关系密切,但M1型小胶质细胞如何作用于神经元导致焦虑样行为并不清楚,因此本研究的目的在于观察小鼠脑内小胶质细胞向M1型极化诱发产生焦虑样行为,并探讨其对神经元树突棘的影响。方法:实验组采用脂多糖(lipopolysaccharide,LPS)脑内注射诱导C57小鼠小胶质细胞向M1型极化,通过旷场实验和高架十字迷宫实验观察小鼠的行为学改变;应用免疫荧光染色方法观察实验组和对照组小鼠的内侧前额叶皮质(medial prefrontal cortex,m PFC)内一氧化氮合酶(i NOS)与小胶质细胞标志物iba-1的表达变化,通过Western Blot方法观察实验组和对照组小鼠的m PFC内i NOS、致炎因子白介素1(IL-1)β、肿瘤坏死因子(TNF)-α的表达变化,以i NOS、IL-1β和TNF-α表达量均显著增加作为小胶质细胞向M1型极化的标志。采用高尔基(Golgi)染色观察m PFC内神经元树突棘的变化。结果:(1)实验组小鼠mPFC内小胶质细胞i NOS、IL-1β和TNF-α表达量均升高,提示小胶质细胞向M1型极化。(2)实验组小鼠在旷场内的中央活动距离和中央活动时间比对照组均明显减少(P0.001);实验组小鼠在高架十字迷宫开臂停留时间比正常组明显减少(P0.05)。(3)Golgi染色结果显示实验组小鼠mPFC内神经元树突棘的密度相较于对照组增多(P0.05)。结论:mPFC内小胶质细胞M1型极化可诱发小鼠产生焦虑样行为,并伴随mPFC内神经元树突棘密度增多,提示脑内小胶质细胞M1型极化可诱导焦虑样行为,可能与内侧前额叶皮质锥体神经元树突棘可塑性改变相关。
[Abstract]:Objective: there is a close relationship between anxiety like behavior and M1 polarization of microglia in brain, but it is not clear how M1 microglia act on neurons to induce anxiety like behavior. The aim of this study was to investigate the effect of microglia on neuronal dendritic spine induced by M1 polarization in mice. Methods: in the experimental group, lipopolysaccharide (LPS) was injected into the brain to induce the microglia of C57 mice to polarize to M1 type, and the behavioral changes were observed by open field test and elevated cross maze test. The expression of nitric oxide synthase (iNOS) and microglia marker (iba-1) in medial prefrontal cortexm of the medial prefrontal cortex of experimental and control mice were observed by immunofluorescence staining. The expression of iNOS- 尾, IL-1IL-1- 尾 and TNF- 伪 in m PFC of experimental and control mice were observed by Western Blot method. The expression of IL-1 尾 and TNF- 伪 was significantly increased as a marker of the polarization of microglia to M1 type. The changes of dendritic spine of neurons in m PFC were observed by Golgi staining. Results (1) the expression of IL-1 尾 and TNF- 伪 in microglia of mPFC in experimental group was increased. These results suggest that the distance and time of central activity in the open field of mice in the experimental group are significantly lower than those in the control group, and the retention time of the mice in the experimental group in the open arm of the elevated cross labyrinth is significantly longer than that in the normal group. The results showed that the density of dendritic spine in mPFC in the experimental group was higher than that in the control group (P 0.05). Conclusion the M 1 polarization of microglia in mPFC can induce anxiety like behavior in mice and increase the density of dendritic spine in mPFC, suggesting that M1 type polarization of microglia in brain can induce anxiety like behavior. It may be related to the plasticity of dendritic spine of pyramidal neurons in medial prefrontal cortex.
【作者单位】：成都医学院基础医学院;第四军医大学神经生物学教研室暨脑科学协同创新中心;第四军医大学学员一旅六营;延安大学生命科学院;
【基金】：国家自然科学基金(81371240)
【分类号】：R749

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