产前应激对子代行为的影响及其机理研究

发布时间：2019-03-26 19:10

【摘要】：产前应激或炎症在大脑一些精神疾病的形成过程中发挥重要作用。产前应激导致的免疫激活,尤其是妊娠后期的免疫激活,能够诱使子代(主要是雄性)的行为、结构和生物化学变化,清楚这种变化的机理对相关精神疾病的治疗具有重要意义。在本文中,我们研究了母体妊娠晚期的应激对雄性子代行为的影响,并探索了可能的机理。我们使用的是妊娠后期模拟病毒免疫激活模型。在怀孕的Wistar rats妊娠的第17天,用模拟病毒poly I:C(polyriboinosinic polyribocytidilic acid)处理,并用生理盐水处理做对照。在雄性子代出生第21天,分别使用生理盐水和不同浓度的pioglitazone(piog,小胶质细胞激活抑制剂)处理,并在第二天检测子代行为。我们使用已知的对精神疾病敏感的认知和行为范例进行测试,如糖水偏好、自主活动、高架十字迷宫和水迷宫。神经炎症的检测是通过RT-PCR检测炎症相关的细胞因子。小胶质细胞的激活则是通过免疫组化确定。实验结果显示用模拟病毒poly I:C处理妊娠晚期的母鼠能够诱导子代神经炎症反应以及抑郁和焦虑样症状。Poly I:C诱导的神经炎症反应是通过检测海马炎性细胞因子IL-1β、IL-6、IFN-γ、CD68、iNOS和TNF-α的增加以及大脑海马的免疫细胞小胶质细胞的激活确定。Poly I:C处理的母鼠子代表现出病态行为,如快感缺乏、站立时间减少、认知功能下降,但用piog处理后的子代则没有明显表现出这些症状。piog能够明显抑制子代海马小胶质细胞形态变化,减少小胶质细胞M1型标记的表达,增加下降的M2型标记的表达。实验结果表明妊娠晚期的母体产前用poly I:C应激会导致子代表现出明显的抑郁和焦虑样行为。这种子代行为异常的机理与大脑海马的免疫激活有关,妊娠晚期的母体应激影响了子代大脑的正常发育,导致子代大脑的免疫激活状态,这最终又导致子代行为异常。使用药物抑制子代大脑的免疫激活能够改善子代的病态行为,这说明抑制或逆转子代大脑的免疫激活是一种有效的大脑免疫相关精神疾病的治疗方法。这对妊娠晚期被感染的母亲后代精神疾病的发生和治疗都具有积极的价值。
[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- 纬, CD68,iNOS and TNF- 伪 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.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714

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