The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901-1573, USA.
Hormone Laboratory Research Group, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Jonas Lies vei 91B, 5021 Bergen, Norway.
Cells. 2023 Sep 21;12(18):2323. doi: 10.3390/cells12182323.
Fetal alcohol spectrum disorders (FASD) are a set of abnormalities caused by prenatal exposure to ethanol and are characterized by developmental defects in the brain that lead to various overt and non-overt physiological abnormalities. Growing evidence suggests that in utero alcohol exposure induces functional and structural abnormalities in gliogenesis and neuron-glia interactions, suggesting a possible role of glial cell pathologies in the development of FASD. However, the molecular mechanisms of neuron-glia interactions that lead to the development of FASD are not clearly understood. In this review, we discuss glial cell pathologies with a particular emphasis on microglia, primary resident immune cells in the brain. Additionally, we examine the involvement of several neuroimmune molecules released by glial cells, their signaling pathways, and epigenetic mechanisms responsible for FASD-related alteration in brain functions. Growing evidence suggests that extracellular vesicles (EVs) play a crucial role in the communication between cells via transporting bioactive cargo from one cell to the other. This review emphasizes the role of EVs in the context of neuron-glia interactions during prenatal alcohol exposure. Finally, some potential applications involving nutritional, pharmacological, cell-based, and exosome-based therapies in the treatment of FASD are discussed.
胎儿酒精谱系障碍（FASD）是一组由产前暴露于乙醇引起的异常，其特征是大脑发育缺陷，导致各种明显和非明显的生理异常。越来越多的证据表明，宫内酒精暴露会诱导神经发生和神经元-胶质细胞相互作用的功能和结构异常，这表明胶质细胞病理学在 FASD 的发展中可能起作用。然而，导致 FASD 发展的神经元-胶质细胞相互作用的分子机制尚不清楚。在这篇综述中，我们讨论了神经胶质细胞病理学，特别强调了小胶质细胞，这是大脑中主要的常驻免疫细胞。此外，我们还研究了几种由神经胶质细胞释放的神经免疫分子的参与，它们的信号通路，以及负责与 FASD 相关的大脑功能改变的表观遗传机制。越来越多的证据表明，细胞外囊泡（EVs）通过将生物活性货物从一个细胞运输到另一个细胞，在细胞间的通讯中发挥着关键作用。这篇综述强调了 EVs 在产前酒精暴露期间神经元-胶质细胞相互作用中的作用。最后，还讨论了一些涉及营养、药理学、基于细胞和基于外泌体的治疗方法在治疗 FASD 中的潜在应用。
