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妊娠和产后早期蛋白质营养不良会破坏猕猴的神经发育。

Gestational and early postnatal protein malnutrition disrupts neurodevelopment in rhesus macaques.

机构信息

Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, United States.

Department of Psychiatry, Oregon Health & Science University, Portland, OR 97239, United States.

出版信息

Cereb Cortex. 2024 Nov 5;34(11). doi: 10.1093/cercor/bhae462.

Abstract

Adequate nutrition during gestation is critical for fetal development, and deficits in protein are associated with neurological and behavioral impairments in offspring placing a significant burden on global health. Fetal and neonatal longitudinal magnetic resonance assessments of brain development spanning mid-gestation to 11 months of age were conducted in rhesus macaque (Macaca mulatta) (n = 22; 9 females) generated from an established nonhuman primate model of gestational protein reduction to ascertain the neurodevelopmental effects of reduced maternal protein intake. Structural abnormalities were identified in two reduced diet groups, in addition to age-dependent whole-brain volume deficits in the most severely reduced (50% vs. 33% reduction) protein cohort, primarily restricted to gray matter structures; i.e. cortical/subcortical gray matter and the cerebellum. Diffusion-weighted imaging revealed widespread postnatal reductions in white matter fractional anisotropy, concentrated in the corpus callosum for both reduced protein levels relative to control diet. Despite extensive neurodevelopmental alterations detectable by longitudinal imaging, early behavioral assessments conducted at 1 month revealed minor perturbations. These results highlight differential impacts of reduced maternal and infant protein intake on gray and white matter formation and organization, with potential implications for early motor development.

摘要

孕期充足的营养对于胎儿发育至关重要,而蛋白质的缺乏与后代的神经和行为损伤有关,这给全球健康带来了巨大负担。在恒河猴(Macaca mulatta)中进行了胎儿和新生儿纵向磁共振脑发育评估,涵盖从中孕期到 11 个月龄,该研究建立了一种非人类灵长类动物模型,用于研究孕期蛋白质减少对脑发育的影响,以确定减少母体蛋白质摄入对神经发育的影响。除了在最严重减少(50%与 33%减少)蛋白质队列中观察到全脑体积随年龄增长的缺陷,主要局限于灰质结构,即皮质/皮质下灰质和小脑外,还在两个低蛋白饮食组中发现了结构异常。弥散加权成像显示,在与对照组相比,两种低蛋白水平的动物的白质各向异性分数在产后均有广泛减少,主要集中在胼胝体。尽管通过纵向成像可以检测到广泛的神经发育改变,但在 1 个月时进行的早期行为评估显示出较小的干扰。这些结果强调了减少母体和婴儿蛋白质摄入对灰质和白质形成和组织的不同影响,这可能对早期运动发育有影响。

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