Maternal immune activation alters placental histone-3 lysine-9 tri-methylation, offspring sensorimotor processing, and hypothalamic transposable element expression in a sex-specific manner.
Maternal immune activation alters placental histone-3 lysine-9 tri-methylation, offspring sensorimotor processing, and hypothalamic transposable element expression in a sex-specific manner.
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DOI：
10.1016/j.ynstr.2023.100538
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发表时间：
2023-05
影响因子：
5
通讯作者：
Kentner, Amanda C.
中科院分区：
文献类型：
--
作者：
DeRosa, Holly;Smith, Arianna;Geist, Laurel;Cheng, Ada;Hunter, Richard G.;Kentner, Amanda C.
关键词：
母体免疫激活（MIA）的动物模型是确定产前感染和神经精神疾病易感性之间相关的生物学机制的核心。然而，许多研究将其范围限制在蛋白质编码基因及其在介导这种固有风险中的作用，而较少关注探索表观基因组和转座因子（TE）的作用。在实验1中，我们证明了MIA改变胎盘染色质景观的能力。腹腔内注射200 μg/kg诱导MIA。脂多糖（LPS）在妊娠第15天的Sprague-Dawley大鼠。我们发现了一个性别特异性的异染色质重排24小时后暴露于MIA，组蛋白-3赖氨酸-9三甲基化（H3 K9 me 3）的增加证明。在实验2中，MIA与长期的感觉运动处理缺陷，减少前脉冲抑制（PPI）的声音惊吓反射在成年男性和女性后代和男性的机械异常性疼痛阈值增加。下丘脑内的基因表达的分析-选择其参与精神分裂症的性别特异性发病机制和应激反应-揭示了显着较高水平的应激敏感基因Gr和Fkbp 5。有害的TE表达通常是神经精神疾病的标志，我们发现几种TE表达的性别特异性增加，包括IAP，B2 SINE和LINE-1 ORF 1。这项研究的数据保证了将来考虑染色质稳定性和TE作为驱动大脑和行为中MIA相关变化的机制的一部分。
Animal models of maternal immune activation (MIA) are central to identifying the biological mechanisms that underly the association between prenatal infection and neuropsychiatric disorder susceptibility. Many studies, however, have limited their scope to protein coding genes and their role in mediating this inherent risk, while much less attention has been directed towards exploring the roles of the epigenome and transposable elements (TEs). In Experiment 1, we demonstrate the ability of MIA to alter the chromatin landscape of the placenta. We induced MIA by injecting 200 μg/kg (i.p.) of lipopolysaccharide (LPS) on gestational day 15 in Sprague-Dawley rats. We found a sex-specific rearrangement of heterochromatin 24-h after exposure to MIA, as evidenced by an increase in histone-3 lysine-9 trimethylation (H3K9me3). In Experiment 2, MIA was associated with long-term sensorimotor processing deficits as indicated by reduced prepulse inhibition (PPI) of the acoustic startle reflex in adult male and female offspring and an increased mechanical allodynia threshold in males. Analyses of gene expression within the hypothalamus-chosen for its involvement in the sex-specific pathogenesis of schizophrenia and the stress response-revealed significantly higher levels of the stress-sensitive genes Gr and Fkbp5. Deleterious TE expression is often a hallmark of neuropsychiatric disease and we found sex-specific increases in the expression of several TEs including IAP, B2 SINE, and LINE-1 ORF1. The data from this study warrant the future consideration of chromatin stability and TEs as part of the mechanism that drives MIA-associated changes in the brain and behavior.
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早期生活节目和神经发育障碍。
影响因子：
10.6
作者：
Bale, Tracy L.;Baram, Tallie Z.;Brown, Alan S.;Goldstein, Jill M.;Insel, Thomas R.;McCarthy, Margaret M.;Nemeroff, Charles B.;Reyes, Teresa M.;Simerly, Richard B.;Susser, Ezra S.;Nestler, Eric J.
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Nestler, Eric J.
影响因子：
5
作者：
Bartlett AA;Guffanti G;Hunter RG
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Hunter RG
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Guffanti G;Bartlett A;Klengel T;Klengel C;Hunter R;Glinsky G;Macciardi F
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Macciardi F
影响因子：
7.3
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通讯作者：
Sinibaldi-Vallebona, Paola
影响因子：
3.3
作者：
Brown, Russell;Imran, Syed A.;Wilkinson, Michael
通讯作者：
Wilkinson, Michael