长期母婴分离会导致小鼠营养不良和全身炎症，同时海马体发育受阻。
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice.
作者信息
Figueiredo Ítalo Leite, Frota Priscila B, da Cunha Davi G, da Silva Raposo Ramon, Canuto Kildere M, de Andrade Geanne M, Sousa Nuno, Moore Sean R, Anstead Gregory M, Alvarez-Leite Jacqueline I, Guerrant Richard L, Oriá Reinaldo B
机构信息
Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Ceara, Brazil.
Experimental Biology Core, Health Center, University of Fortaleza, Ceara, Brazil.
出版信息
Nutrition. 2016 Sep;32(9):1019-27. doi: 10.1016/j.nut.2016.02.016. Epub 2016 Mar 6.
OBJECTIVE
Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in 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.
METHODS
This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (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 (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study.
RESULTS
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 reduced hippocampal aspartate, glutamate, and gamma-aminobutyric acid levels, as compared with unseparated controls.
CONCLUSION
These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.
目的
出生后前2周的长期母婴分离（PMS）与生长发育不良有关，并对脑结构和功能产生持久影响。本研究旨在调查PMS诱导的营养不良是否会导致全身炎症以及营养相关激素水平的变化，从而影响C57BL/6J乳鼠的海马结构和神经传递。
方法
本研究评估了小鼠的生长参数以及胰岛素样生长因子-1（IGF-1）的血清水平。此外，还测量了PMS后瘦素、脂联素和皮质酮的血清水平。同时评估了海马体的立体结构和氨基酸水平。此外，我们还测量了全脑组织中髓鞘碱性蛋白和突触素（SYN）的表达以及海马体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情况。通过每天将每窝幼崽中的一半与哺乳母鼠分离特定时间（第1天4小时，第2天8小时，此后每天12小时）来诱导PMS。本研究共使用了67只乳鼠。
结果
PMS导致体重增加显著减缓及生长发育受损。PMS后血清瘦素和IGF-1水平显著降低。PMS小鼠的总CA3区面积和体积减小，尤其影响锥体层。CA1锥体层面积也减小。整体海马体SYN免疫标记较低，特别是在CA3区和齿状回。此外，与未分离的对照组相比，PMS降低了海马体中天冬氨酸、谷氨酸和γ-氨基丁酸的水平。
结论
这些发现表明，PMS会导致显著的生长缺陷以及海马体形态和神经传递的改变。
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