de la Monte Suzanne M, Tong Ming, Ziplow Jason, Mark Princess, Van Stephanie, Nguyen Van Ahn
Departments of Pathology and Laboratory Medicine, Neurosurgery, and Neurology, Rhode Island Hospital, Providence, RI 02903, USA.
Women & Infants Hospital, Brown University Health, Providence, RI 02905, USA.
Nutrients. 2025 Feb 26;17(5):812. doi: 10.3390/nu17050812.
Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties. : To determine if dietary soy interventions during pregnancy would be sufficient to normalize central nervous system structure and function, we examined the effects of maternal gestation-limited dietary soy on cerebellar postnatal development, motor function, and critical signaling pathways. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source. The ethanol and soy feedings were discontinued upon delivery. The offspring were subjected to rotarod motor function tests, and on postnatal day 35, they were sacrificed to harvest cerebella for histological and molecular studies. Despite the postnatal cessation of alcohol exposure, chronic gestational exposure reduced brain weight, caused cerebellar hypoplasia, and impaired motor performance. Gestational dietary soy prevented the ethanol-associated reduction in brain weight and largely restored the histological integrity of the cerebellum but failed to normalize motor performance. Ethanol withdrawal abolished the impairments in insulin/IGF signaling that were previously associated with ongoing ethanol exposures, but ethanol's inhibitory effects on Notch and Wnt signaling persisted. Soy significantly increased cerebellar expression of the insulin and IGF-1 receptors and abrogated several ethanol-associated impairments in Notch and Wnt signaling. Although gestation-restricted dietary soy has significant positive effects on neurodevelopment, optimum prevention of FASD's long-term effects will likely require dietary soy intervention during the critical periods of postnatal development, even after alcohol exposures have ceased.
产前酒精暴露（PAE）模型可导致神经发育异常，类似于胎儿酒精谱系障碍（FASD）中观察到的情况。先前的研究将大脑中实验性PAE效应与胰岛素/胰岛素样生长因子（IGF）和Notch信号通路受损联系起来，这些信号通路介导神经元存活、生长、迁移、能量代谢和可塑性。重要的是，同时给予过氧化物酶体增殖物激活受体激动剂或膳食大豆可预防FASD的许多方面，这归因于它们的胰岛素增敏、抗炎和抗氧化特性。为了确定孕期膳食大豆干预是否足以使中枢神经系统结构和功能正常化，我们研究了孕期有限期膳食大豆对小脑产后发育、运动功能和关键信号通路的影响。给怀孕的Long Evans大鼠喂食等热量的液体饮食，其中含有0%或26%热量的乙醇，以酪蛋白或大豆分离物作为蛋白质来源。分娩后停止乙醇和大豆喂养。对后代进行转棒运动功能测试，并在出生后第35天处死，以收获小脑用于组织学和分子研究。尽管产后停止了酒精暴露，但慢性孕期暴露仍降低了脑重量，导致小脑发育不全，并损害了运动性能。孕期膳食大豆可防止乙醇相关的脑重量减轻，并在很大程度上恢复小脑的组织学完整性，但未能使运动性能正常化。戒酒消除了先前与持续乙醇暴露相关的胰岛素/IGF信号通路损伤，但乙醇对Notch和Wnt信号通路的抑制作用仍然存在。大豆显著增加了小脑胰岛素和IGF-1受体的表达，并消除了Notch和Wnt信号通路中几种与乙醇相关的损伤。尽管孕期受限的膳食大豆对神经发育有显著的积极影响，但即使在酒精暴露停止后，要最佳预防FASD的长期影响，可能仍需要在产后发育的关键时期进行膳食大豆干预。
