Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity
Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity
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DOI：
10.1073/pnas.191369798
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Misner, DL;Jacobs, S;Evans, RM
尽管它有很长的历史，但在成年小鼠中，维生素A逐渐枯竭的核心影响以前还没有被描述过。一项对缺乏维生素的动物的研究显示，海马区CA1区的长期增强能力逐渐受到严重损害，长期抑郁实际上已经消失。重要的是，这些损失是完全可逆的，通过体内补充维生素A饮食或直接将所有反式维甲酸应用于急性海马片。我们发现维甲酸反应性转基因在海马体中高度活跃，通过使用解剖的外植体，我们展示了海马体是一个强大的合成生物活性维甲酸的场所。综上所述，这些结果表明，维生素A及其活性衍生物是成人大脑中长期突触可塑性的基本能力因子，并表明长期增强和长期抑郁所需的关键基因是维甲酸依赖的。这些数据表明，对数亿缺乏维生素A的成年人和儿童来说，这是一个重大的心理后果。
Despite its long history, the central effects of progressive depletion of vitamin A in adult mice has not been previously described. An examination of vitamin-deprived animals revealed a progressive and ultimately profound impairment of hippocampal CA1 longterm potentiation and a virtual abolishment of long-term depression. Importantly, these losses are fully reversible by dietary vitamin A replenishment in vivo or direct application of all trans-retinoic acid to acute hippocampal slices. We find retinoid responsive transgenes to be highly active in the hippocampus, and by using dissected explants, we show the hippocampus to be a site of robust synthesis of bioactive retinoids. In aggregate, these results demonstrate that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain, and suggest that key genes required for long-term potentiation and long-term depression are retinoid dependent. These data suggest a major mental consequence for the hundreds of millions of adults and children who are vitamin A deficient.