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子宫内环境和母体行为对产前创伤小鼠模型神经内分泌及行为改变的影响

Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma.

作者信息

Golub Y, Canneva F, Funke R, Frey S, Distler J, von Hörsten S, Freitag C M, Kratz O, Moll G H, Solati J

机构信息

Department of Child and Adolescent Mental Health, University Clinic Erlangen, Schwabachanlage 6 und 10, 91054, Erlangen, Germany.

Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, Goethe University Hospital Frankfurt, Deutschordenstrasse 50, 60528 Frankfurt am Main, Germany.

出版信息

Dev Neurobiol. 2016 Nov;76(11):1254-1265. doi: 10.1002/dneu.22387. Epub 2016 Mar 9.

DOI:10.1002/dneu.22387
PMID:26899175
Abstract

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016.

摘要

孕期创伤暴露后母亲患创伤后应激障碍(PTSD)与儿童情感障碍风险增加有关。为了研究产前创伤和/或母亲PTSD影响大脑发育和行为的机制,我们基于在妊娠第12天对C57Bl/6N雌性小鼠孕期施加电足电击,建立了产前创伤(PT)经历的小鼠模型。该模型基于先前验证的PTSD动物模型。我们发现,母亲创伤(MT)后,母鼠焦虑水平高、母性关怀差,同时血清催乳素降低、皮质酮水平升高。PT幼崽出生时体型较小,且一生都保持较小体型。我们发现,在出生后第9天(PND 9)与母亲分离时,PT幼崽发出超声波叫声的时间和频率增加。交叉寄养实验表明,与由MT母鼠抚养的未经历创伤的幼崽相比,由健康母亲抚养的PT幼崽焦虑水平较低。重要的是,与其他实验组相比,产前创伤和由受过创伤的母亲抚养相结合会导致:(1)幼崽皮质酮水平最高,(2)超声波叫声时间最长,(3)焦虑水平最高。我们的数据表明,MT后母性关怀有明显变化,这可能与创伤导致的催乳素水平下降有关。此外,我们表明,母亲行为对后代焦虑的发展至关重要,母性关怀的特定方面在很大程度上覆盖了子宫内和产后环境的影响。© 2016威利期刊公司。《发育神经生物学》76: 1254 - 1265,2016年。

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