Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory.
Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory.
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青春期过量的叶酸会抑制甲状腺功能，导致动机和空间记忆永久性缺陷。
DOI：
10.1111/j.1601-183x.2011.00749.x
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Redei,EE
中科院分区：
文献类型：
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作者：
Sittig,LJ;Herzing,LBK;Xie,H;Batra,KK;Shukla,PK;Redei,EE
膳食叶酸缺乏可能导致或加剧认知和记忆缺陷，通过在谷物和膳食补充剂中添加叶酸可以解决这一问题。对于青少年和非怀孕成人，B9 维生素叶酸的推荐剂量为 400 微克/天，摄入量超过推荐的每日摄入量并不被认为是有害的。然而，过量叶酸的影响尚未在青春期进行过测试，因为青春期的神经和内分泌发育表明可能容易受到长期认知影响。我们给 30 至 60 天龄的随意喂食的大鼠喂食叶酸补充剂（8.0 毫克叶酸/千克饮食）或对照实验室饲料（2.7 毫克叶酸/千克饮食），随后在莫里斯水迷宫中测试它们的动机以及学习和记忆能力。我们发现补充叶酸的动物存在动机和空间记忆缺陷，但它们的海马中与学习和记忆相关的分子生长相关蛋白-43或Gs-α亚基蛋白没有变化。他们的外周甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平降低，海马甲状腺受体-α1和-α2（TRα1和TRα2）的蛋白质水平降低。后者可能是由于在假定的甲状腺激素受体-α启动子内观察到胞嘧啶-磷酸-鸟苷岛甲基化的增加，这是我们首次在大鼠中绘制的。总体而言，青春期补充叶酸会导致动机和空间记忆缺陷，这可能是由外周和海马甲状腺激素功能受到抑制所介导的。
Cognitive and memory deficits can be caused or exacerbated by dietary folate deficiency, which has been combatted by the addition of folate to grains and dietary supplements. The recommended dose of the B9 vitamin folate is 400 µg/day for adolescents and non‐pregnant adults, and consumption above the recommended daily allowance is not considered to be detrimental. However, the effects of excess folate have not been tested in adolescence when neuro and endocrine development suggest possible vulnerability to long‐term cognitive effects. We administered folate‐supplemented (8.0 mg folic acid/kg diet) or control lab chow (2.7 mg folic acid/kg diet) to ratsad libitumfrom 30 to 60 days of age, and subsequently tested their motivation and learning and memory in the Morris water maze. We found that folate‐supplemented animals had deficits in motivation and spatial memory, but they showed no changes of the learning‐ and memory‐related molecules growth‐associated protein‐43 or Gs‐αsubunit protein in the hippocampus. They had decreased levels of thyroxine (T4) and triiodothyronine (T3) in the periphery and decreased protein levels of thyroid receptor‐α1 and ‐α2 (TRα1 and TRα2) in the hippocampus. The latter may have been due to an observed increase of cytosine–phosphate–guanosine island methylation within the putative thyroid hormone receptor‐αpromoter, which we have mapped for the first time in the rat. Overall, folate supplementation in adolescence led to motivational and spatial memory deficits that may have been mediated by suppressed thyroid hormone function in the periphery and hippocampus.