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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