Prenatal alcohol exposure alters mRNA expression for stress peptides, glucocorticoid receptor function and immune factors in acutely stressed neonatal brain.
Prenatal alcohol exposure alters mRNA expression for stress peptides, glucocorticoid receptor function and immune factors in acutely stressed neonatal brain.
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DOI：
10.3389/fnins.2023.1203557
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发表时间：
2023
影响因子：
4.3
通讯作者：
Milligan, Erin D. D.
中科院分区：
文献类型：
--
作者：
Ruffaner-Hanson, Chaselyn D. D.;Fernandez-Oropeza, Annette K. K.;Sun, Melody S. S.;Caldwell, Kevin K. K.;Allan, Andrea M. M.;Savage, Daniel D. D.;Valenzuela, C. Fernando;Noor, Shahani;Milligan, Erin D. D.
杏仁核、海马和下丘脑是重要的应激调节区域，其经历最初在妊娠期和出生后早期脑发育期间建立的应激反应的功能成熟。胎儿酒精谱系障碍（FASD）是产前酒精暴露（PAE）的结果，可导致认知、情绪和行为障碍。产前酒精暴露会对大脑应激反应系统的组成部分产生负面影响，包括杏仁核、海马和下丘脑中与应激相关的大脑神经肽和糖皮质激素受体。虽然PAE产生独特的脑细胞因子表达模式，但对Toll样受体4（TLR 4）和相关促炎信号传导因子以及PAE脑应激反应区域中的抗炎细胞因子的作用知之甚少。我们假设PAE使早期脑应激反应系统敏感，导致神经内分泌和神经免疫激活失调。在雄性和雌性出生后第10天（PND 10）C57 B1/6后代中使用单次4小时母体分离应激暴露。后代来自产前控制暴露（糖精）或有限的访问（4小时）在黑暗中饮酒的PAE模型。在PND 10应激后立即收集海马、杏仁核和下丘脑，分析应激相关因子的mRNA表达（CRH和AVP），糖皮质激素受体信号调节剂（GAS 5、FKBP 51和FKBP 52）、星形胶质细胞和小胶质细胞活化，以及与TLR 4活化相关的因子，包括促炎性白细胞介素-1 β（IL-1β），沿着额外的促炎和抗炎细胞因子。对CRH、FKBP和与来自男性和女性杏仁核的TLR 4信号级联相关的因子进行选择性蛋白表达分析。女性杏仁核显示应激相关因子、糖皮质激素受体信号调节因子和TLR 4激活级联反应中所有关键因子的mRNA表达增加，而下丘脑显示应激后PAE中所有这些因子的mRNA表达减弱。相反，在男性中观察到的mRNA变化要少得多，特别是在海马体和下丘脑，但杏仁核没有。在患有PAE的雄性后代中观察到CRH蛋白的统计学显著性增加和IL-1β增加的强烈趋势，与应激源暴露无关。产前酒精暴露会产生压力相关因素和TLR-4神经免疫通路致敏作用，主要在女性中观察到，这在出生后早期的压力挑战中被揭露。
The amygdala, hippocampus and hypothalamus are critical stress regulatory areas that undergo functional maturation for stress responding initially established during gestational and early postnatal brain development. Fetal alcohol spectrum disorder (FASD), a consequence of prenatal alcohol exposure (PAE), results in cognitive, mood and behavioral disorders. Prenatal alcohol exposure negatively impacts components of the brain stress response system, including stress-associated brain neuropeptides and glucocorticoid receptors in the amygdala, hippocampus and hypothalamus. While PAE generates a unique brain cytokine expression pattern, little is known about the role of Toll-like receptor 4 (TLR4) and related proinflammatory signaling factors, as well as anti-inflammatory cytokines in PAE brain stress-responsive regions. We hypothesized that PAE sensitizes the early brain stress response system resulting in dysregulated neuroendocrine and neuroimmune activation. A single, 4-h exposure of maternal separation stress in male and female postnatal day 10 (PND10) C57Bl/6 offspring was utilized. Offspring were from either prenatal control exposure (saccharin) or a limited access (4 h) drinking-in-the-dark model of PAE. Immediately after stress on PND10, the hippocampus, amygdala and hypothalamus were collected, and mRNA expression was analyzed for stress-associated factors (CRH and AVP), glucocorticoid receptor signaling regulators (GAS5, FKBP51 and FKBP52), astrocyte and microglial activation, and factors associated with TLR4 activation including proinflammatory interleukin-1β (IL-1β), along with additional pro- and anti-inflammatory cytokines. Select protein expression analysis of CRH, FKBP and factors associated with the TLR4 signaling cascade from male and female amygdala was conducted. The female amygdala revealed increased mRNA expression in stress-associated factors, glucocorticoid receptor signaling regulators and all of the factors critical in the TLR4 activation cascade, while the hypothalamus revealed blunted mRNA expression of all of these factors in PAE following stress. Conversely, far fewer mRNA changes were observed in males, notably in the hippocampus and hypothalamus, but not the amygdala. Statistically significant increases in CRH protein, and a strong trend in increased IL-1β were observed in male offspring with PAE independent of stressor exposure. Prenatal alcohol exposure creates stress-related factors and TLR-4 neuroimmune pathway sensitization observed predominantly in females, that is unmasked in early postnatal life by a stress challenge.
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影响因子：
3.7
作者：
Przybycien-Szymanska MM;Mott NN;Pak TR
通讯作者：
Pak TR
影响因子：
3.5
作者：
Lussier AA;Bodnar TS;Moksa M;Hirst M;Kobor MS;Weinberg J
通讯作者：
Weinberg J
影响因子：
2.9
作者：
Caldwell KK;Hafez A;Solomon E;Cunningham M;Allan AM
通讯作者：
Allan AM
DOI：
10.2165/00066982-200307030-00008
发表时间：
2003-01-01
期刊：
Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology
影响因子：
--
作者：
Bottero, Virginie;Imbert, Veronique;Peyron, Jean-Francois
通讯作者：
Peyron, Jean-Francois
影响因子：
9.3
作者：
Bodnar, Tamara S.;Raineki, Charlis;Weinberg, Joanne
通讯作者：
Weinberg, Joanne