Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice.
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice.
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DOI：
10.1016/j.nut.2016.02.016
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Oriá RB
中科院分区：
文献类型：
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作者：
Figueiredo ÍL;Frota PB;da Cunha DG;da Silva Raposo R;Canuto KM;de Andrade GM;Sousa N;Moore SR;Anstead GM;Alvarez-Leite JI;Guerrant RL;Oriá RB
在出生后的前两周内，长期的母亲分离（PMS）与大脑结构和功能的长期影响有关。本研究旨在探讨经前综合症诱导的营养不良是否会导致C57 BL/6 J乳鼠全身炎症和营养相关激素水平的变化，从而影响海马结构和神经传递。本研究评估了小鼠生长参数和IGF-1血清水平。此外，血清瘦素，脂联素和皮质酮水平测定后PMS。还评估了海马体视学和氨基酸水平。此外，我们测量了髓鞘碱性蛋白和突触素（SYN）的表达在整个脑组织和海马SYN免疫标记。对于行为测试，我们分析了选定的新生儿反射的个体发育。通过每天将每窝中一半幼仔与其泌乳期母体分离规定时间（第1天4 h，第2天8 h，此后12 h）诱导PMS。本研究共使用了67只哺乳幼仔。经前综合症引起体重增加和生长障碍的显着放缓。经前综合征患者血清瘦素和IGF-1水平显著降低。总CA 3面积和体积减少，特别是影响PMS小鼠的锥体层。CA 1锥体层面积也减少。整体海马SYN免疫标记较低，尤其是在CA 3区和齿状回。此外，与未分离的对照组相比，PMS降低海马天冬氨酸、谷氨酸和GABA水平。总之，这些研究结果表明，经前综合症导致显着的生长缺陷和海马形态和神经传递的改变。
Prolonged maternal separation (PMS) in the first two weeks of life has been associated with poor growth with lasting effects in the brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. This study assessed mouse growth parameters coupled with IGF-1 serum levels. In addition, leptin, adiponectin and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4h on day 1, 8h on day 2, and 12h thereafter). A total of 67 suckling pups were used in this study. PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduces hippocampal aspartate, glutamate, and GABA levels, as compared with unseparated controls. Altogether, these findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.