小膠質(zhì)細(xì)胞M1型極化誘發(fā)小鼠焦慮樣行為及其對前額葉神經(jīng)元樹突棘密度的影響
本文選題:小膠質(zhì)細(xì)胞極化 + 焦慮樣行為。 參考:《神經(jīng)解剖學(xué)雜志》2017年04期
【摘要】:目的:焦慮樣行為與腦內(nèi)小膠質(zhì)細(xì)胞M1型極化關(guān)系密切,但M1型小膠質(zhì)細(xì)胞如何作用于神經(jīng)元導(dǎo)致焦慮樣行為并不清楚,因此本研究的目的在于觀察小鼠腦內(nèi)小膠質(zhì)細(xì)胞向M1型極化誘發(fā)產(chǎn)生焦慮樣行為,并探討其對神經(jīng)元樹突棘的影響。方法:實驗組采用脂多糖(lipopolysaccharide,LPS)腦內(nèi)注射誘導(dǎo)C57小鼠小膠質(zhì)細(xì)胞向M1型極化,通過曠場實驗和高架十字迷宮實驗觀察小鼠的行為學(xué)改變;應(yīng)用免疫熒光染色方法觀察實驗組和對照組小鼠的內(nèi)側(cè)前額葉皮質(zhì)(medial prefrontal cortex,m PFC)內(nèi)一氧化氮合酶(i NOS)與小膠質(zhì)細(xì)胞標(biāo)志物iba-1的表達(dá)變化,通過Western Blot方法觀察實驗組和對照組小鼠的m PFC內(nèi)i NOS、致炎因子白介素1(IL-1)β、腫瘤壞死因子(TNF)-α的表達(dá)變化,以i NOS、IL-1β和TNF-α表達(dá)量均顯著增加作為小膠質(zhì)細(xì)胞向M1型極化的標(biāo)志。采用高爾基(Golgi)染色觀察m PFC內(nèi)神經(jīng)元樹突棘的變化。結(jié)果:(1)實驗組小鼠mPFC內(nèi)小膠質(zhì)細(xì)胞i NOS、IL-1β和TNF-α表達(dá)量均升高,提示小膠質(zhì)細(xì)胞向M1型極化。(2)實驗組小鼠在曠場內(nèi)的中央活動距離和中央活動時間比對照組均明顯減少(P0.001);實驗組小鼠在高架十字迷宮開臂停留時間比正常組明顯減少(P0.05)。(3)Golgi染色結(jié)果顯示實驗組小鼠mPFC內(nèi)神經(jīng)元樹突棘的密度相較于對照組增多(P0.05)。結(jié)論:mPFC內(nèi)小膠質(zhì)細(xì)胞M1型極化可誘發(fā)小鼠產(chǎn)生焦慮樣行為,并伴隨mPFC內(nèi)神經(jīng)元樹突棘密度增多,提示腦內(nèi)小膠質(zhì)細(xì)胞M1型極化可誘導(dǎo)焦慮樣行為,可能與內(nèi)側(cè)前額葉皮質(zhì)錐體神經(jīng)元樹突棘可塑性改變相關(guān)。
[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- 偽 in m PFC of experimental and control mice were observed by Western Blot method. The expression of IL-1 尾 and TNF- 偽 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- 偽 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.
【作者單位】: 成都醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)院;第四軍醫(yī)大學(xué)神經(jīng)生物學(xué)教研室暨腦科學(xué)協(xié)同創(chuàng)新中心;第四軍醫(yī)大學(xué)學(xué)員一旅六營;延安大學(xué)生命科學(xué)院;
【基金】:國家自然科學(xué)基金(81371240)
【分類號】:R749
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