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早期补充微量营养素可预防早期应激诱导的认知障碍。

Early micronutrient supplementation protects against early stress-induced cognitive impairments.

作者信息

Naninck Eva F G, Oosterink J Efraim, Yam Kit-Yi, de Vries Lennart P, Schierbeek Henk, van Goudoever Johannes B, Verkaik-Schakel Rikst-Nynke, Plantinga Josèe A, Plosch Torsten, Lucassen Paul J, Korosi Aniko

机构信息

Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.

Department of Mother and Child, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.

出版信息

FASEB J. 2017 Feb;31(2):505-518. doi: 10.1096/fj.201600834R. Epub 2016 Oct 21.

Abstract

Early-life stress (ES) impairs cognition later in life. Because ES prevention is problematic, intervention is needed, yet the mechanisms that underlie ES remain largely unknown. So far, the role of early nutrition in brain programming has been largely ignored. Here, we demonstrate that essential 1-carbon metabolism-associated micronutrients (1-CMAMs; i.e., methionine and B vitamins) early in life are crucial in programming later cognition by ES. ES was induced in male C57Bl/6 mice from postnatal d (P)2-9. 1-CMAM levels were measured centrally and peripherally by using liquid chromatography-mass spectroscopy. Next, we supplemented the maternal diet with 1-CMAM only during the ES period and studied cognitive, neuroendocrine, neurogenic, transcriptional, and epigenetic changes in adult offspring. We demonstrate that ES specifically reduces methionine in offspring plasma and brain. Of note, dietary 1-CMAM enrichment during P2-9 restored methionine levels and rescued ES-induced adult cognitive impairments. Beneficial effects of this early dietary enrichment were associated with prevention of the ES-induced rise in corticosterone and adrenal gland hypertrophy did not involve changes in maternal care, hippocampal volume, neurogenesis, or global/Nr3c1-specific DNA methylation. In summary, nutrition is important in brain programming by ES. A short, early supplementation with essential micronutrients can already prevent lasting effects of ES. This concept opens new avenues for nutritional intervention.-Naninck, E. F. G., Oosterink, J. E., Yam, K.-Y., de Vries, L. P., Schierbeek, H., van Goudoever, J. B., Verkaik-Schakel, R.-N., Plantinga, J. A., Plosch, T., Lucassen, P. J., Korosi, A. Early micronutrient supplementation protects against early stress-induced cognitive impairments.

摘要

早年生活应激(ES)会损害晚年的认知能力。由于预防ES存在问题,因此需要进行干预,但ES背后的机制在很大程度上仍不为人知。到目前为止,早期营养在大脑编程中的作用在很大程度上被忽视了。在这里,我们证明,生命早期与一碳代谢相关的必需微量营养素(1-CMAMs,即蛋氨酸和B族维生素)在ES对后期认知的编程中至关重要。从出生后第2天(P)到第9天,在雄性C57Bl/6小鼠中诱导ES。通过液相色谱-质谱法在中枢和外周测量1-CMAM水平。接下来,我们仅在ES期间在母鼠饮食中补充1-CMAM,并研究成年后代的认知、神经内分泌、神经发生、转录和表观遗传变化。我们证明,ES会特异性降低后代血浆和大脑中的蛋氨酸水平。值得注意的是,在P2-9期间饮食中富含1-CMAM可恢复蛋氨酸水平,并挽救ES诱导的成年认知障碍。这种早期饮食强化的有益效果与预防ES诱导的皮质酮升高和肾上腺肥大有关,且不涉及母性关怀、海马体积、神经发生或整体/Nr3c1特异性DNA甲基化的变化。总之,营养在ES对大脑的编程中很重要。早期短期补充必需微量营养素已经可以预防ES的持久影响。这一概念为营养干预开辟了新途径。-纳宁克,E.F.G.,奥斯特林克,J.E.,任,K.-Y.,德弗里斯,L.P.,席尔贝克,H.,范古多弗,J.B.,韦尔凯克-沙克尔,R.-N.,普兰廷加,J.A.,普洛施,T.,卢卡森,P.J.,科罗西,A.早期微量营养素补充可预防早期应激诱导的认知障碍。

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