Department of Anatomy, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi, 464-8650, Japan.
Department of Life Science, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Sci Rep. 2017 Jul 10;7(1):4934. doi: 10.1038/s41598-017-04289-1.
Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that arise from prenatal exposure to ethanol (EtOH). However, detailed reports regarding the adverse effects of prenatal EtOH exposure on neocortical morphology and its underlying pathogenic mechanisms are limited. In the present study, we aimed to characterize the anatomical abnormalities of neocortical development and their correlation with microglial properties and neuro-inflammation in a mouse model of FASD. We evaluated the development and maturation of the neocortex in ICR mice prenatally exposed to 25% (w/v) EtOH using histological and molecular analyses. Reduced proliferation and excessive cell death were observed in the dorsal telencephalon. Abnormal neuronal distribution, layer formation, and dopaminergic neuronal projections were observed in the neocortex. Disruption of microglial differentiation (M1/M2 microglial ratio) and abnormal expression of pro-inflammatory and neurotrophic factors were induced, and these abnormalities were ameliorated by co-treatment with an anti-inflammatory drug (pioglitazone). FASD model mice displayed histological abnormalities, microglial abnormalities, and neuro-inflammation in both the embryonic and newborn stages. Thus, anti-inflammatory therapeutics may provide a novel preventive approach for the treatment of FASD.
胎儿酒精谱系障碍 (FASD) 是一组由胎儿期暴露于乙醇 (EtOH) 引起的多种疾病。然而，关于产前 EtOH 暴露对新皮层形态及其潜在发病机制的不良影响的详细报告有限。在本研究中，我们旨在描述 FASD 小鼠模型中新皮层发育的解剖结构异常及其与小胶质细胞特性和神经炎症的相关性。我们使用组织学和分子分析评估了 ICR 小鼠在产前暴露于 25%（w/v）EtOH 时的新皮层发育和成熟情况。在背侧端脑中观察到增殖减少和细胞死亡过度。在新皮层中观察到异常的神经元分布、层形成和多巴胺能神经元投射。诱导小胶质细胞分化（M1/M2 小胶质细胞比例）异常和促炎和神经营养因子的异常表达，并通过用抗炎药物（吡格列酮）进行联合治疗来改善这些异常。FASD 模型小鼠在胚胎期和新生儿期均显示出组织学异常、小胶质细胞异常和神经炎症。因此，抗炎治疗可能为治疗 FASD 提供一种新的预防方法。
