Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation
Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation
复制标题
DOI：
10.1016/j.bbi.2014.04.005
复制
发表时间：
2014-08-01
影响因子：
15.1
通讯作者：
Meyer, Urs
中科院分区：
文献类型：
--
作者：
Giovanoli, Sandra;Weber, Liz;Meyer, Urs
产前感染和青春期生活中的创伤经历是发育性神经精神障碍的两个环境危险因素。在翻译动物模型中模拟这些因素对神经元的累积影响，导致最近确定了这些环境逆境在成人脑功能障碍发展中的病理相互作用。本研究探讨的后果相结合的产前免疫挑战和围青春期应激离散细胞异常的γ-氨基丁酸（GABA）系统的海马。用病毒模拟物poly（I：C）（=polyriboinosinic-polyribocytidilic add）或对照溶液处理怀孕小鼠，然后在青春期发育期间不受干扰地或经受不可预测的亚慢性应激，所述子代出生于暴露于poly（I：C）或对照的母体。小清蛋白表达细胞的体视学估计显示，暴露于联合免疫激活和应激的成年后代的腹侧齿状回中这些GABA能中间神经元显著减少。单次暴露于任一环境因素不足以引起类似的神经病理学。我们进一步发现，青春期应激对海马背角（CA）区域的reelin免疫反应细胞产生相反的影响，应激分别增加和减少对照后代和产前免疫挑战动物的reelin表达。目前的数据表明，两种环境风险因素的组合，其中每一个都涉及主要神经精神疾病的病因，诱导海马GABA能细胞群的显着，但有限的神经病理学影响，已知受影响的大脑疾病与神经发育组件。(C)2014爱思唯尔公司All rights reserved.
Exposure to prenatal infection and traumatizing experiences in peripubertal life are two environmental risk factors for developmental neuropsychiatric disorders. Modeling the cumulative neuronal impact of these factors in a translational animal model has led to the recent identification of pathological interactions between these environmental adversities in the development of adult brain dysfunctions. The present study explored the consequences of combined prenatal immune challenge and peripubertal stress on discrete cellular abnormalities in the gamma-aminobutyric acid (GABA) system of the hippocampus. Pregnant mice were treated with the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic add) or control solution, and offspring born to poly(I:C)-exposed or control mothers were then left undisturbed or subjected to unpredictable sub-chronic stress during peripubertal development. Stereological estimations of parvalbumin-expressing cells revealed a significant reduction of these GABAergic interneurons in the ventral dentate gyrus of adult offspring exposed to combined immune activation and stress. Single exposure to either environmental factor was insufficient to cause similar neuropathology. We further found that peripubertal stress exerted opposite effects on reelin-immunoreactive cells in the dorsal cornu ammonis (CA) region of the hippocampus, with stress increasing and decreasing reelin expression in control offspring and prenatally immune challenged animals, respectively. The present data suggest that the combination of two environmental risk factors, which have each been implicated in the etiology of major neuropsychiatric disease, induces significant but restricted neuropathological effects on hippocampal GABAergic cell populations known to be affected in brain disorders with neurodevelopmental components. (C) 2014 Elsevier Inc. All rights reserved.