Mice Born to Mothers with Gravida Traumatic Brain Injury Have Distorted Brain Circuitry and Altered Immune Responses.
Mice Born to Mothers with Gravida Traumatic Brain Injury Have Distorted Brain Circuitry and Altered Immune Responses.
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患有妊娠创伤性脑损伤的母亲所生的小鼠的大脑回路扭曲并改变了免疫反应。
DOI：
10.1089/neu.2021.0048
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发表时间：
2021
影响因子：
4.2
通讯作者：
Lifshitz,Jonathan
中科院分区：
文献类型：
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作者：
Saber,Maha;Ortiz,JBryce;RojasValencia,LuisaM;Ma,Xiaokuang;Tallent,BretR;Adelson,PDavid;Rowe,RachelK;Qiu,Shenfeng;Lifshitz,Jonathan
亲密伴侣暴力（IPV）增加了创伤性脑损伤（TBI）的风险。在怀孕期间，身体攻击的频率和强度都会增加。妊娠期脑外伤（妊娠期脑外伤；gTBI）对后代发育的影响尚不清楚，妊娠期的应激和炎症会使胎儿发育结果恶化。我们假设，与对照组母亲所生的小鼠相比，gTBI会导致混合性后代的焦虑和抑郁相关行为增加，炎症反应和肠道病理改变，以及脑回路扭曲。交配后12天，孕鼠分别接受弥漫性脑损伤或假性损伤（对照组）。我们发现，雄性gTBI后代是gTBI对健康、生理和行为影响的主要驱动因素。例如，gTBI的雄性（而非雌性）后代在断奶时的体重明显低于对照雄性后代。出生后28天，gTBI子代与对照子代相比，其与第5层前额锥体神经元的层内连通性明显减弱。与对照组相比，gTBI后代在焦虑类行为方面的神经学表现有所下降，在抑郁类行为方面只有微小差异。在PND42和PND58时，gTBI雄性后代的循环中性粒细胞和单核细胞数量明显少于对照雄性后代。在随后的PND75炎症反应中，gTBI后代的循环中性粒细胞数量明显小于对照组后代。在gTBI后代的免疫挑战期间，焦虑样行为持续存在。然而，脾脏免疫反应和肠道组织学在两组间无显著差异。这些结果迫使进一步的研究来确定gTBI对胎儿和母体结局的全部程度。
Intimate partner violence (IPV) increases risk of traumatic brain injury (TBI). Physical assaults increase in frequency and intensity during pregnancy. The consequences of TBI during pregnancy (gravida TBI; gTBI) on offspring development is unknown, for which stress and inflammation during pregnancy worsen fetal developmental outcomes. We hypothesized that gTBI would lead to increased anxiety- and depression-related behavior, altered inflammatory responses and gut pathology, and distorted brain circuitry in mixed-sex offspring compared to mice born to control mothers. Pregnant dams received either diffuse TBI or sham injury (control) 12 days post-coitum. We found that male gTBI offspring were principal drivers of the gTBI effects on health, physiology, and behavior. For example, male, but not female, gTBI offspring weighed significantly less at weaning compared to male control offspring. At post-natal day (PND) 28, gTBI offspring had significantly weaker intralaminar connectivity onto layer 5 pre-frontal pyramidal neurons compared to control offspring. Neurological performance on anxiety-like behaviors was decreased, with only marginal differences in depressive-like behaviors, for gTBI offspring compared to control offspring. At PND42 and PND58, circulating neutrophil and monocyte populations were significantly smaller in gTBI male offspring than control male offspring. In response to a subsequent inflammatory challenge at PND75, gTBI offspring had significantly smaller circulating neutrophil populations than control offspring. Anxiety-like behaviors persisted during the immune challenge in gTBI offspring. However, spleen immune response and gut histology showed no significant differences between groups. The results compel further studies to determine the full extent of gTBI on fetal and maternal outcomes.