Prenatal choline supplementation advances hippocampal development and enhances MAPK and CREB activation
Prenatal choline supplementation advances hippocampal development and enhances MAPK and CREB activation
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DOI：
10.1096/fj.03-0877fje
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Blusztajn, JK
中科院分区：
文献类型：
--
作者：
Mellott, TJ;Williams, CL;Blusztajn, JK
胆碱是动物和人类必需的营养素。先前的研究表明，在大鼠怀孕的后半期，在母鼠的饮食中补充胆碱可以永久地提高成年后代的记忆表现。本研究表明，产前补充胆碱可以使幼年大鼠在水迷宫任务中使用关系线索的能力提高3天，表明这种治疗加速了海马的成熟。此外，在谷氨酸、n-甲基- d -天冬氨酸或K+去极化浓度的刺激下，海马有丝分裂原激活蛋白激酶（MAPK）和camp反应元件结合蛋白（CREB）的磷酸化和活化会因产前补充胆碱而增加，而因产前胆碱缺乏而减少。这些数据首次证明了海马MAPK和CREB信号通路的发育可塑性是由胎儿发育过程中单一必需营养素胆碱的供应控制的，并指出这些通路是产前补充胆碱诱导的发育和长期认知增强的候选机制。
Choline is an essential nutrient for animals and humans. Previous studies showed that supplementing the maternal diet with choline during the second half of gestation in rats permanently enhances memory performance of the adult offspring. Here we show that prenatal choline supplementation causes a 3-day advancement in the ability of juvenile rats to use relational cues in a water maze task, indicating that the treatment accelerates hippocampal maturation. Moreover, phosphorylation and therefore activation of hippocampal mitogen-ctivated protein kinase (MAPK) and cAMP-response element binding protein (CREB) in response to stimulation by glutamate, N-methyl-D-aspartate, or depolarizing concentrations of K+ were increased by prenatal choline supplementation and reduced by prenatal choline deficiency. These data provide the first evidence that developmental plasticity of the hippocampal MAPK and CREB signaling pathways is controlled by the supply of a single essential nutrient, choline, during fetal development and point to these pathways as candidate mechanisms for the developmental and long-term cognitive enhancement induced by prenatal choline supplementation.