Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice
Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice
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DOI：
10.1016/j.bbi.2012.11.013
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发表时间：
2013-02-01
影响因子：
15.1
通讯作者：
Garcia-Segura, Luis M.
中科院分区：
文献类型：
--
作者：
Diz-Chaves, Yolanda;Astiz, Mariana;Garcia-Segura, Luis M.
早期的生活经历，如产前应激，可能会导致神经和免疫系统功能的永久性改变。在这项研究中，我们评估了产前应激是否影响成年雄性小鼠对炎性挑战时海马区的炎症反应。将妊娠C57BL/6小鼠随机分为应激组和非应激组。应激组动物从妊娠第12天至分娩，放置在透明塑料圆筒中，每天照射3次，每次45min。没有应激反应的怀孕小鼠没有受到干扰。在4个月龄时，在全身注射脂多糖(LPS)或赋形剂后24小时，处死无应激和产前应激的雄性后代。在基础条件下，与未应激的雄性动物相比，产前应激大鼠海马区白介素1β和肿瘤坏死因子-α的表达增加，CA1区具有反应性形态的小胶质细胞百分比增加。此外，胎儿期应激小鼠在注射脂多糖后，心肌细胞内的肿瘤坏死因子-α免疫反应增强，齿状回内Iba-1免疫反应阳性的小胶质细胞和胶质纤维酸性蛋白阳性星形胶质细胞的数量增加。相比之下，在非应激动物中，脂多糖不会引起这样的变化。这些发现表明，产前应激在成年期诱导了海马区基础的促炎状态，导致小胶质细胞和星形胶质细胞对促炎损伤的反应增强。(C)2012 Elsevier Inc.保留所有权利。
Early life experiences, such as prenatal stress, may result in permanent alterations in the function of the nervous and immune systems. In this study we have assessed whether prenatal stress affects the inflammatory response of the hippocampal formation of male mice to an inflammatory challenge during adulthood. Pregnant C57BL/6 mice were randomly assigned to stress (n = 10) or non-stress (n = 10) groups. Animals of the stress group were placed in plastic transparent cylinders and exposed to bright light for 3 sessions of 45 min every day from gestational day 12 to parturition. Non-stressed pregnant mice were left undisturbed. At four months of age, non stressed and prenatally stressed male offspring were killed, 24 h after the systemic administration of lipopolysaccharide (LPS) or vehicle. Under basal conditions, prenatally stressed animals showed increased expression of interleukin 1 beta and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and an increased percentage of microglia cells with reactive morphology in CA1 compared to non-stressed males. Furthermore, prenatally stressed mice showed increased TNF-alpha immunoreactivity in CM and increased number of Iba-1 immunoreactive microglia and GFAP-immunoreactive astrocytes in the dentate gyrus after LPS administration. In contrast, LPS did not induce such changes in non-stressed animals. These findings indicate that prenatal stress induces a basal proinflammatory status in the hippocampal formation during adulthood that results in an enhanced activation of microglia and astrocytes in response to a proinflammatory insult. (C) 2012 Elsevier Inc. All rights reserved.