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早期生活免疫刺激对行为反应的性别差异:小胶质细胞和星形胶质细胞的参与。

The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement.

机构信息

Laboratory of Genetic, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofail University, Kenitra. Morocco.

Instituto Cajal, C.S.I.C, Madrid, Spain.

出版信息

Physiol Behav. 2019 Feb 1;199:386-394. doi: 10.1016/j.physbeh.2018.11.037. Epub 2018 Dec 7.

Abstract

It is well known that inflammatory challenge during the prenatal period results in permanent changes in glial cells and behavior in adulthood. However, it is unknown whether inflammatory challenge during the infantile period may have permanent sexually-dimorphic effects on microglia and astrocytes in vivo, which in turn may be associated with sex differences in adult behavior. In this study, we have evaluated whether postnatal injection of lipopolysaccharide (LPS; 250μg/kg, i.p. on postnatal day 14) induces depressive and less anxiety-like behaviors, glial cell activation, pro-inflammatory cytokine (TNF-alpha) secretion and sexually dimorphic responses in adulthood. Postnatal day 14 (P14) male and female Wistar rats received an intraperitoneal (ip) injection of LPS or PBS. Three months later, animals were tested in the Open Field (OF), the Elevated Plus Maze (EPM) and the Forced Swimming Test (FST) to assess the level of anxiety and depression-like behavior. Hippocampal proinflammatory cytokine TNF-alpha concentration and the number of astrocytes and microglia were estimated in the dentate gyrus, CA1, and CA3 in two regions of the hippocampus (ventral and dorsal). Our results showed that the administration of LPS resulted in less anxiety and depression-like behavior in males but not in females. However, the LPS-administration increased the number of microglia in the dorsal and ventral hippocampus areas in females more than male, while no significant differences in TNFα level had been detected between the LPS-rats treated and their controls. Interestingly, LPS resulted in an increase in the number of astrocytes in both areas of the hippocampus in a female. While in a male, our results showed a decrease in astrocytes number in the dorsal hippocampus, but no significant differences observed in ventral hippocampus. These findings indicate that an immune challenge in infantile rats induces a ventral and dorsal hippocampus damage in female more than in male, without affecting significantly the affective behavior changes in the female. The results also showed that small changes in the male hippocampus can affect the behavior and induce a depression-like behavior.

摘要

众所周知,孕期炎症刺激会导致成年后神经胶质细胞永久性变化和行为改变。然而,目前尚不清楚婴儿期的炎症刺激是否会对体内小胶质细胞和星形胶质细胞产生永久性的性别二态影响,而这些影响又可能与成年后行为的性别差异有关。在这项研究中,我们评估了在产后第 14 天(PND14)腹腔内注射脂多糖(LPS;250μg/kg)是否会诱导成年后抑郁和焦虑样行为减少、神经胶质细胞激活、促炎细胞因子(TNF-α)分泌和性别二态反应。PND14 雄性和雌性 Wistar 大鼠接受 LPS 或 PBS 腹腔内(ip)注射。三个月后,动物在旷场(OF)、高架十字迷宫(EPM)和强迫游泳试验(FST)中进行测试,以评估焦虑和抑郁样行为水平。在海马的齿状回、CA1 和 CA3 两个区域估计海马内促炎细胞因子 TNF-α浓度和星形胶质细胞和小胶质细胞数量。我们的结果表明,LPS 给药导致雄性而非雌性动物焦虑和抑郁样行为减少。然而,LPS 给药增加了雌性海马背侧和腹侧区域小胶质细胞的数量,而 LPS 处理的大鼠和对照组之间的 TNFα 水平没有显著差异。有趣的是,LPS 导致雌性海马的两个区域的星形胶质细胞数量增加。而在雄性中,我们的结果显示,背侧海马的星形胶质细胞数量减少,但在腹侧海马没有观察到显著差异。这些发现表明,幼年大鼠的免疫挑战会导致雌性海马的背侧和腹侧区域损伤,而对雌性的情感行为变化没有显著影响。研究结果还表明,雄性海马的微小变化会影响行为并诱导类似抑郁的行为。

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