Neuronal miR-17-5p contributes to interhemispheric cortical connectivity defects induced by prenatal alcohol exposure,Cell Reports

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Neuronal miR-17-5p contributes to interhemispheric cortical connectivity defects induced by prenatal alcohol exposure
Cell Reports ( IF 7.5 ) Pub Date : 2023-08-22 , DOI: 10.1016/j.celrep.2023.113020
Mike Altounian ₁ , Anaïs Bellon ₂ , Fanny Mann ₁

Affiliation

Structural and functional deficits in brain connectivity are reported in patients with fetal alcohol spectrum disorders (FASDs), but whether and how prenatal alcohol exposure (PAE) affects axonal development of neurons and disrupts wiring between brain regions is unknown. Here, we develop a mouse model of moderate alcohol exposure during prenatal brain wiring to study the effects of PAE on corpus callosum (CC) development. PAE induces aberrant navigation of interhemispheric CC axons that persists even after exposure ends, leading to ectopic termination in the contralateral cortex. The neuronal miR-17-5p and its target ephrin type A receptor 4 (EphA4) mediate the effect of alcohol on the contralateral targeting of CC axons. Thus, altered microRNA-mediated regulation of axonal guidance may have implications for interhemispheric cortical connectivity and associated behaviors in FASD.

中文翻译：

神经元 miR-17-5p 导致产前酒精暴露引起的半球间皮质连接缺陷

据报道，患有胎儿酒精谱系障碍 (FASD) 的患者存在大脑连接的结构和功能缺陷，但产前酒精暴露 (PAE) 是否以及如何影响神经元的轴突发育并破坏大脑区域之间的连接尚不清楚。在这里，我们开发了一种在产前大脑连接期间适度酒精暴露的小鼠模型，以研究 PAE 对胼胝体 (CC) 发育的影响。PAE 会引起半球间 CC 轴突的异常导航，即使在暴露结束后这种异常导航仍然存在，导致对侧皮质异位终止。神经元 miR-17-5p 及其靶标肝配蛋白 A 型受体 4 (EphA4) 介导酒精对 CC 轴突对侧靶向的影响。因此，改变 microRNA 介导的轴突引导调节可能对 FASD 的半球间皮质连接和相关行为产生影响。

更新日期：2023-08-22

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