Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006.
Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97214.
Proc Natl Acad Sci U S A. 2020 May 5;117(18):10035-10044. doi: 10.1073/pnas.1919048117. Epub 2020 Apr 20.
One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.
导致胎儿酒精谱系障碍（FASD）高发的一个因素是在怀孕前意识到之前的暴饮式酒精消费。众所周知，早期识别 FASD 可以提高治疗效果。最近，用于重建三维（3D）胎儿脑 MRI 的回溯运动校正技术取得了进展，这显著提高了胎儿脑的解剖和扩散 MRI 的质量和分辨率。在这里，我们使用了一种涉及在怀孕前每天口服 1.5 g/kg 乙醇并持续到 168 天妊娠期的第 60 天的恒河猴 FASD 模型，以确定胎儿 MRI 是否可以检测到酒精对脑发育的影响。该方法在妊娠第 135 天（G135）发现了暴露于乙醇的胎儿和对照组之间的差异，但在 G110 或 G85 天没有发现差异。在 G135 时，与对照组相比，暴露于乙醇的胎儿的脑干和小脑体积以及几个白质束的水扩散各向异性降低。在 MRI 后立即从胎儿脑组织上进行的离体电生理记录表明，在 G135 观察到的结构异常具有功能意义。具体而言，从初级体感皮层和壳核中的单个神经元测量的自发兴奋性突触后电流幅度与连接这些结构的白质束的扩散各向异性强烈相关。这些发现表明，在妊娠早期暴露于乙醇会以可通过胎儿 MRI 检测到的方式扰乱与运动控制相关的脑区的发育。
