【摘要】：產(chǎn)前應(yīng)激或炎癥在大腦一些精神疾病的形成過程中發(fā)揮重要作用。產(chǎn)前應(yīng)激導(dǎo)致的免疫激活,尤其是妊娠后期的免疫激活,能夠誘使子代(主要是雄性)的行為、結(jié)構(gòu)和生物化學(xué)變化,清楚這種變化的機(jī)理對(duì)相關(guān)精神疾病的治療具有重要意義。在本文中,我們研究了母體妊娠晚期的應(yīng)激對(duì)雄性子代行為的影響,并探索了可能的機(jī)理。我們使用的是妊娠后期模擬病毒免疫激活模型。在懷孕的Wistar rats妊娠的第17天,用模擬病毒poly I:C(polyriboinosinic polyribocytidilic acid)處理,并用生理鹽水處理做對(duì)照。在雄性子代出生第21天,分別使用生理鹽水和不同濃度的pioglitazone(piog,小膠質(zhì)細(xì)胞激活抑制劑)處理,并在第二天檢測(cè)子代行為。我們使用已知的對(duì)精神疾病敏感的認(rèn)知和行為范例進(jìn)行測(cè)試,如糖水偏好、自主活動(dòng)、高架十字迷宮和水迷宮。神經(jīng)炎癥的檢測(cè)是通過RT-PCR檢測(cè)炎癥相關(guān)的細(xì)胞因子。小膠質(zhì)細(xì)胞的激活則是通過免疫組化確定。實(shí)驗(yàn)結(jié)果顯示用模擬病毒poly I:C處理妊娠晚期的母鼠能夠誘導(dǎo)子代神經(jīng)炎癥反應(yīng)以及抑郁和焦慮樣癥狀。Poly I:C誘導(dǎo)的神經(jīng)炎癥反應(yīng)是通過檢測(cè)海馬炎性細(xì)胞因子IL-1β、IL-6、IFN-γ、CD68、iNOS和TNF-α的增加以及大腦海馬的免疫細(xì)胞小膠質(zhì)細(xì)胞的激活確定。Poly I:C處理的母鼠子代表現(xiàn)出病態(tài)行為,如快感缺乏、站立時(shí)間減少、認(rèn)知功能下降,但用piog處理后的子代則沒有明顯表現(xiàn)出這些癥狀。piog能夠明顯抑制子代海馬小膠質(zhì)細(xì)胞形態(tài)變化,減少小膠質(zhì)細(xì)胞M1型標(biāo)記的表達(dá),增加下降的M2型標(biāo)記的表達(dá)。實(shí)驗(yàn)結(jié)果表明妊娠晚期的母體產(chǎn)前用poly I:C應(yīng)激會(huì)導(dǎo)致子代表現(xiàn)出明顯的抑郁和焦慮樣行為。這種子代行為異常的機(jī)理與大腦海馬的免疫激活有關(guān),妊娠晚期的母體應(yīng)激影響了子代大腦的正常發(fā)育,導(dǎo)致子代大腦的免疫激活狀態(tài),這最終又導(dǎo)致子代行為異常。使用藥物抑制子代大腦的免疫激活能夠改善子代的病態(tài)行為,這說明抑制或逆轉(zhuǎn)子代大腦的免疫激活是一種有效的大腦免疫相關(guān)精神疾病的治療方法。這對(duì)妊娠晚期被感染的母親后代精神疾病的發(fā)生和治療都具有積極的價(jià)值。
[Abstract]:Prenatal stress or inflammation plays an important role in the development of some mental disorders in the brain. Pre-natal stress-induced immune activation, especially in the late trimester of pregnancy, can induce behavioral, structural and biochemical changes in offspring (mainly males). It is of great significance to understand the mechanism of this change for the treatment of related mental diseases. In this paper, we studied the effect of maternal stress on the behavior of male offspring in the third trimester of pregnancy, and explored the possible mechanism. We used a late-trimester model of viral immune activation. On the 17th day of pregnancy, Wistar rats was treated with simulated virus poly I / C (polyriboinosinic polyribocytidilic acid) and normal saline as control. On the 21st day of birth, the male offspring were treated with saline and different concentrations of pioglitazone (piog, microglial activation inhibitor respectively, and the offspring behavior was detected on the next day. We used known cognitive and behavioral paradigms that were sensitive to mental illness, such as sugar-water preferences, autonomic activity, elevated labyrinths and water labyrinths. The detection of neuroinflammation is the detection of inflammation-related cytokines by RT-PCR. The activation of microglia is determined by immunohistochemistry. The results showed that poly I C could induce neuroinflammatory responses and depression and anxiety-like symptoms in the third trimester of pregnancy. The neuroinflammatory response induced by Poly I C was through the detection of IL-1 尾 in the hippocampus. The increase of IL-6,IFN- 緯, CD68,iNOS and TNF- 偽 and the activation of microglia in the hippocampus of the brain indicate that the mothers and daughters treated with Poly I 尾 C represent abnormal behavior, such as lack of pleasure and decrease in standing time. The cognitive function decreased, but the offspring treated with piog did not show these symptoms. Piog could significantly inhibit the morphological changes of microglia and decrease the expression of M1-labeled microglia in the offspring. Increased the down-regulated M2 marker expression. The results showed that prenatal poly I C stress in the third trimester of pregnancy resulted in significant depression and anxiety-like behavior. The mechanism of the abnormal behavior of the offspring is related to the immune activation of the hippocampus. Maternal stress in the third trimester of pregnancy affects the normal development of the brain of the offspring, leading to the immune activation of the brain of the offspring, which in turn leads to the abnormal behavior of the offspring. The use of drugs to inhibit the immune activation of the offspring brain can improve the abnormal behavior of the offspring, which indicates that the inhibition or reversal of the immune activation of the offspring brain is an effective therapy for brain immune-related mental disorders. This is of positive value in the occurrence and treatment of mental illness among infected mothers and offspring in late trimester of pregnancy.
【學(xué)位授予單位】：電子科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R714

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