Fetal alcohol spectrum disorders and neuroimmune changes.
Fetal alcohol spectrum disorders and neuroimmune changes.
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DOI：
10.1016/b978-0-12-801284-0.00003-8
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发表时间：
2014
影响因子：
--
通讯作者：
Kane, Cynthia J. M.
中科院分区：
文献类型：
--
作者：
Drew, Paul D.;Kane, Cynthia J. M.
胎儿酒精谱系障碍（FASD）的行为后果是严重的，并且终生持续存在。FASD的致病机制知之甚少。然而，从人类结构和功能研究以及动物模型中已经了解了很多关于FASD的信息，这些研究提供了对FASD潜在机制的更好理解。使用FASD的动物模型，最近发现乙醇诱导发育中的大脑中的神经免疫激活。由此产生的小胶质细胞活化、促炎分子的产生和发育基因表达的改变被认为会改变神经元的存活和功能，并导致长期的神经病理学和认知缺陷。还发现发生小胶质细胞损失，降低了小胶质细胞保护神经元和促进神经元发育的能力。这一点很重要，因为新的证据表明，大脑发育过程中的小胶质细胞耗竭会导致长期的神经病理和认知缺陷。有趣的是，胎儿大脑中小胶质细胞耗竭和神经免疫激活的行为后果与FASD特别相关。本章回顾了FASD的神经病理和行为异常，并在动物模型中描述了相关性。这是讨论神经免疫系统在正常大脑发育中的作用，小胶质细胞耗竭和神经炎症的后果，FASD动物模型中乙醇诱导神经炎症过程的证据，以及开发抗炎疗法作为预防或治疗FASD的新策略的基础。总之，这些知识为讨论和进一步研究FASD中神经免疫过程的作用提供了一个框架。
The behavioral consequences of fetal alcohol spectrum disorders (FASD) are serious and persist throughout life. The causative mechanisms underlying FASD are poorly understood. However, much has been learned about FASD from human structural and functional studies as well as from animal models, which have provided a greater understanding of the mechanisms underlying FASD. Using animal models of FASD, it has been recently discovered that ethanol induces neuroimmune activation in the developing brain. The resulting microglial activation, production of proinflammatory molecules, and alteration in expression of developmental genes are postulated to alter neuron survival and function and lead to long-term neuropathological and cognitive defects. It has also been discovered that microglial loss occurs, reducing microglia’s ability to protect neurons and contribute to neuronal development. This is important, because emerging evidence demonstrates that microglial depletion during brain development leads to long-term neuropathological and cognitive defects. Interestingly, the behavioral consequences of microglial depletion and neuroimmune activation in the fetal brain are particularly relevant to FASD. This chapter reviews the neuropathological and behavioral abnormalities of FASD and delineates correlates in animal models. This serves as a foundation to discuss the role of the neuroimmune system in normal brain development, the consequences of microglial depletion and neuroinflammation, the evidence of ethanol induction of neuroinflammatory processes in animal models of FASD, and the development of anti-inflammatory therapies as a new strategy for prevention or treatment of FASD. Together, this knowledge provides a framework for discussion and further investigation of the role of neuroimmune processes in FASD.