Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation.

Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation.
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DOI:
10.1007/s12035-014-8856-9
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发表时间:
2015-08
影响因子:
5.1
通讯作者:
Wang B
Wang B
中科院分区:
医学2区
文献类型:
--
作者:
Chen Y;Zheng Z;Zhu X;Shi Y;Tian D;Zhao F;Liu N;Hüppi PS;Troy FA 2nd;Wang B

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乳铁蛋白(Lf)是一种富含唾液酸(Sia)的铁结合乳糖蛋白,具有多种功能的健康益处。它在神经发育和认知中的潜在作用尚不清楚。为了验证Lf可能具有改善神经发育和认知功能的假设,在第3 ~ 38天的仔猪饲粮中添加Lf。定量测定所选基因的表达水平及其同源蛋白谱。我们的新发现的重要性在于,Lf(1)上调了与神经发育和认知相关的几种典型信号通路;(2)影响海马中涉及脑源性神经营养因子(BDNF)信号通路的约10个基因,上调多唾液酸的表达,多唾液酸是神经可塑性、祖细胞的细胞迁移和分化以及轴突生长和靶向性的标志;(3) BDNF转录和翻译水平上调,环腺苷单磷酸(cAMP)反应元件结合蛋白(CREB)磷酸化增加,CREB是BDNF信号通路的下游靶点,是神经发育和认知中至关重要的蛋白;(4)在八臂径向迷宫中增强仔猪的认知功能和学习能力。Lf可以改善出生后仔猪的神经发育和认知能力,这一发现以前没有报道过。本文的在线版本(doi:10.1007/s12035-014-8856-9)包含补充资料,仅供授权用户使用。
Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits. Its potential role in neurodevelopment and cognition remains unknown. To test the hypothesis that Lf may function to improve neurodevelopment and cognition, the diet of postnatal piglets was supplemented with Lf from days 3 to 38. Expression levels of selected genes and their cognate protein profiles were quantitatively determined. The importance of our new findings is that Lf (1) upregulated several canonical signaling pathways associated with neurodevelopment and cognition; (2) influenced ~10 genes involved in the brain-derived neurotrophin factor (BDNF) signaling pathway in the hippocampus and upregulated the expression of polysialic acid, a marker of neuroplasticity, cell migration and differentiation of progenitor cells, and the growth and targeting of axons; (3) upregulated transcriptional and translational levels of BDNF and increased phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, a downstream target of the BDNF signaling pathway, and a protein of crucial importance in neurodevelopment and cognition; and (4) enhanced the cognitive function and learning of piglets when tested in an eight-arm radial maze. The finding that Lf can improve neural development and cognition in postnatal piglets has not been previously described. The online version of this article (doi:10.1007/s12035-014-8856-9) contains supplementary material, which is available to authorized users.