Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and antioxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GAD67GFP+ interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence (GE), the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized DHE oxidation levels in GE and ameliorated the migration delay caused by prenatal stress. Through convergent redox manipula-tions, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.

中文翻译：

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氧化还原失调在产前应激对胚胎中间神经元迁移的影响中的作用。


怀孕期间母亲的压力与后代精神疾病的风险增加有关，但产前压力破坏的胚胎大脑机制尚不完全清楚。我们的实验室表明，产前应激会延迟抑制性神经祖细胞的迁移。在这里，我们研究了氧化还原失调作为胚胎皮质中间神经元迁移延迟的机制，利用直接操作抗氧化剂和抗氧化剂以及从胚胎第 12 天开始的母体重复约束应激小鼠模型。迁移 GAD67GFP+ 中间神经元的延时实时成像显示抑制性祖细胞的正常切向迁移被促氧化剂过氧化氢破坏。子宫内脑室内鱼藤酮也延迟了中间神经元的迁移。产前应激改变了谷胱甘肽水平，并诱导胚胎前脑中抗氧化酶活性和氧化还原相关基因表达的变化。对产前应激后神经节隆起 (GE)（迁移中间神经元的来源）中二氢乙锭 (DHE) 荧光的评估显示，DHE 氧化水平增加。母体抗氧化剂（N-乙酰半胱氨酸和虾青素）使 GE 中的 DHE 氧化水平正常化，并改善了产前应激引起的迁移延迟。通过聚合氧化还原操作，发现产前应激后的中间神经元迁移延迟与氧化还原失调密切相关。产前时期的氧化还原生物学可能是保护大脑发育的目标。