Retinoic acid receptors move in time with the clock in the hippocampus. Effect of a vitamin-A-deficient diet.
Retinoic acid receptors move in time with the clock in the hippocampus. Effect of a vitamin-A-deficient diet.
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DOI：
10.1016/j.jnutbio.2012.05.006
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Anzulovich AC
中科院分区：
文献类型：
--
作者：
Navigatore-Fonzo LS;Golini RL;Ponce IT;Delgado SM;Plateo-Pignatari MG;Gimenez MS;Anzulovich AC
内源性计时机制控制哺乳动物的昼夜生物节律。以前，我们表明，维生素A缺乏症修改时钟BMAL 1和PER 1以及BDNF和神经颗粒蛋白的日常节律在大鼠海马，当动物保持在12小时光照：12小时黑暗的条件下。视黄酸核受体，RAR和RXR，已在同一脑区检测到。本研究的目的是：1）分析大鼠海马RARα、RARβ和RXRβ是否具有昼夜节律性变化; 2）研究维生素A缺乏饮食对BMAL 1、PER 1和视黄酸受体（RAR s和RXRβ）基因昼夜表达的影响。在治疗的最后一周期间，将来自对照组和维生素A缺乏组的Holtzman雄性大鼠维持在12小时光照：12小时黑暗或12小时黑暗：12小时黑暗下。在24 h内每4 h分离海马样品，测定RARα、RARβ、RXRβ、BMAL 1和PER 1的转录和蛋白水平。扫描RAR和RXRβ基因的调控区以寻找时钟响应位点，同时分析BMAL 1和PER 1启动子的RARE和RXRE。E-box和RORE位点位于维甲酸受体基因的调控区，在大鼠海马中显示内源性控制的昼夜节律表达。当动物喂食维生素A缺乏的饮食时，这些时间曲线被修改。类似地，营养性维生素A缺乏使BMAL 1相移，并在mRNA和蛋白质水平上消除PER 1昼夜节律表达。我们的数据表明，维生素A缺乏可能会影响昼夜节律的表达在海马通过修改节奏的视黄酸受体。
An endogenous time-keeping mechanism controls circadian biological rhythms in mammals. Previously, we showed that the vitamin A deficiency modifies clock BMAL1 and PER1 as well as BDNF and Neurogranin daily rhythmicity in the rat hippocampus, when animals are maintained under 12h-light:12h-dark conditions. Retinoic acid nuclear receptors, RARs and RXRs, have been detected in the same brain area. Our objectives were 1) to analyze whether RARα, RARβ and RXRβ exhibit a circadian variation in the rat hippocampus, 2) to investigate the effect of a vitamin A-deficient diet on the circadian expression of BMAL1, PER1 and retinoic acid receptors (RARs and RXRβ) genes. Holtzman male rats from control and vitamin A-deficient groups were maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARα, RARβ, RXRβ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRβ genes were scanned for clock-responsive sites while BMAL1 and PER1 promoters were analyzed for RAREs and RXREs. E-box and RORE sites were found on regulatory regions of retinoid receptors genes, which display an endogenously-controlled circadian expression in the rat hippocampus. Those temporal profiles were modified when animals were fed with a vitamin A-deficient diet. Similarly, the nutritional vitamin A deficiency phase shifted BMAL1 and abolished PER1 circadian expression at both, mRNA and protein levels. Our data suggests that the vitamin A deficiency may affect the circadian expression in the hippocampus by modifying the rhythmic profiles of retinoic acid receptors.
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影响因子：
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作者：
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