Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders.
Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders.
复制标题
DOI：
10.1016/j.expneurol.2017.07.002
复制
发表时间：
2018-01
影响因子：
5.3
通讯作者：
Tran PK
中科院分区：
文献类型：
--
作者：
Bilbo SD;Block CL;Bolton JL;Hanamsagar R;Tran PK
免疫分子，如细胞因子和趋化因子以及在大脑中产生它们的细胞，特别是小胶质细胞，对正常的大脑发育至关重要。近年来，这种认识导致了一种工作假设，即怀孕期间的炎症事件，例如对感染的反应，可能会在神经发育的关键阶段破坏免疫分子的正常表达，从而导致神经发育障碍的风险，如自闭症谱系障碍（ASD）。这一假设在很大程度上受到了Paul Patterson博士及其同事的工作的指导，他们优雅地证明了对怀孕小鼠的单一病毒感染或病毒模拟物的注射显著且持续地影响后代的免疫和神经系统功能，这些变化是ASD样行为功能障碍的基础，包括社交和沟通障碍。许多实验室在人类和非人类动物模型中的后续研究支持了以下假设，即持续破坏的免疫分子表达和/或神经炎症至少有助于ASD的重要子集。在ASD中观察到的异质性临床和生物学表型强烈表明，在遗传易感个体中，环境风险因素联合收割机或协同作用产生功能障碍的临界点或阈值点。重要的是，动物研究显示母体免疫激活（MIA）与后代ASD样结果之间存在联系，涉及与人类ASD相关的不同物种和多种环境因素，除了感染，包括毒素暴露，母体压力和母体肥胖，所有这些都会影响炎症或免疫途径。本次审查的目标是突出帕特森博士的工作对自闭症领域的更广泛的影响，重点是MIA由不同的环境因素对胎儿大脑发育，免疫系统发育和ASD的病理生理的影响。
Immune molecules such as cytokines and chemokines and the cells that produce them within the brain, notably microglia, are critical for normal brain development. This recognition has in recent years led to the working hypothesis that inflammatory events during pregnancy, e.g. in response to infection, may disrupt the normal expression of immune molecules during critical stages of neural development and thereby contribute to the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). This hypothesis has in large part been shepherded by the work of Dr. Paul Patterson and colleagues, which has elegantly demonstrated that a single viral infection or injection of a viral mimetic to pregnant mice significantly and persistently impacts offspring immune and nervous system function, changes that underlie ASD-like behavioral dysfunction including social and communication deficits. Subsequent studies by many labs – in humans and in non-human animal models - have supported the hypothesis that ongoing disrupted immune molecule expression and/or neuroinflammation contributes to at least a significant subset of ASD. The heterogeneous clinical and biological phenotypes observed in ASD strongly suggest that in genetically susceptible individuals, environmental risk factors combine or synergize to create a tipping or threshold point for dysfunction. Importantly, animal studies showing a link between maternal immune activation (MIA) and ASD-like outcomes in offspring involve different species and diverse environmental factors associated with ASD in humans, beyond infection, including toxin exposures, maternal stress, and maternal obesity, all of which impact inflammatory or immune pathways. The goal of this review is to highlight the broader implications of Dr. Patterson's work for the field of autism, with a focus on the impact that MIA by diverse environmental factors has on fetal brain development, immune system development, and the pathophysiology of ASD.
登录
查看更多内容
影响因子：
15.1
作者：
Bolton, Jessica L.;Auten, Richard L.;Bilbo, Staci D.
通讯作者：
Bilbo, Staci D.
影响因子：
5.3
作者：
Bilbo, SD;Biedenkapp, JC;Maier, SF
通讯作者：
Maier, SF
影响因子：
3
作者：
Bilbo SD;Schwarz JM
通讯作者：
Schwarz JM
影响因子：
15.9
作者：
Block, Michelle L.;Calderon-Garciduenas, Lilian
通讯作者：
Calderon-Garciduenas, Lilian
影响因子：
6.2
作者：
Bilbo, Staci D.;Smith, Susan H.;Schwarz, Jaclyn M.
通讯作者：
Schwarz, Jaclyn M.