Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation

被引:62
作者
Giovanoli, Sandra [1 ]
Weber, Liz [1 ]
Meyer, Urs [1 ]
机构
[1] Swiss Fed Inst Technol, Physiol & Behav Lab, CH-8603 Schwerzenbach, Switzerland
基金
瑞士国家科学基金会;
关键词
Animal model; Autism; Cytokines; GABA; Infection; Inflammation; Stress; Schizophrenia; BIPOLAR DISORDER; ANIMAL-MODEL; SCHIZOPHRENIA; BRAIN; DYSREGULATION; INTERNEURONS; PREGNANCY; MICE; PATHOPHYSIOLOGY; INFLAMMATION;
D O I
10.1016/j.bbi.2014.04.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:48 / 54
页数:7
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