Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.
Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.
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DOI：
10.1016/j.neuroscience.2014.09.008
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发表时间：
2014-11-07
期刊：
影响因子：
3.3
通讯作者：
Saito, M.
中科院分区：
文献类型：
--
作者：
Sadrian, B.;Lopez-Guzman, M.;Wilson, D. A.;Saito, M.
妊娠期接触酒精会导致长期行为缺陷，通常被称为胎儿酒精谱系障碍 (FASD)。 FASD 模型啮齿动物急性乙醇暴露研究通常选择一个发育窗口来模拟相当于人类胚胎发生的特定环境，并研究该特定发育时期内乙醇暴露的后果。暴露时间可能是早期乙醇暴露神经行为后果的一个重要决定因素，因为每个大脑区域对乙醇细胞毒性的敏感性不同，并且在其发育过程中具有独特的敏感期。我们对雄性和雌性小鼠胚胎第 8 天 (E8) 或出生后第 7 天 (P7) 的单日暴食乙醇的长期影响进行了平行比较，并在此证明了具有截然不同发育轨迹的两个系统对神经解剖学、行为和体内电生理学的不同长期影响。由于发育期乙醇暴露而发现，嗅觉-海马通路中大脑区域之间的气味诱发活动、局部回路抑制和自发一致性方面存在显着的长期差异，并根据刺激时间的不同而变化。还发现对细胞增殖和中间神经元细胞密度的长期影响因损伤时间和区域而异。最后，暴露于 P7 的小鼠的空间记忆表现受到影响，但暴露于 E8 的小鼠则没有受到影响。我们的生理学和行为结果在概念上与从这些相同小鼠获得的神经解剖学数据是一致的。我们的结果认识到乙醇暴露时间对长期电路功能及其支持行为的可变和共同影响。
Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance was affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior.
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