Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Transl Psychiatry. 2021 Mar 2;11(1):149. doi: 10.1038/s41398-021-01274-1.
Maternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.
母体环境暴露，如高脂肪饮食、糖尿病和肥胖症，可对子代产生长期影响。这些影响包括神经发育障碍（NDD）的风险增加，包括自闭症谱系障碍（ASD）、抑郁和焦虑。这些晚年神经效应的机制尚不清楚。在本文中，我们测量了后代大脑的变化，并确定了哪些大脑区域对母体代谢环境敏感，因此可能介导 NDD 风险。我们表明，尽管在断奶时被切换到低脂饮食，但暴露于高脂肪饮食的小鼠在成年期仍表现出广泛的大脑变化。受早期饮食影响的大脑区域包括扩展的杏仁核系统，它在寻求奖励行为中起着重要作用。在这些区域中优先表达的基因具有与进食行为相关的功能，同时也与人类 NDD 有关，如自闭症。我们的数据表明，早期暴露于高脂肪饮食的母体可导致大脑发生改变，即使在饮食改变后，这些改变也会持续到成年期。
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