Retinoic acid receptors move in time to the clock in the hippocampus. Effect of a vitamin A-deficient diet

NAVIGATORE FONZO, LORENA; GOLINI R; PONCE I.T; DELGADO S.M; PLATEO G; GIMENEZ, M S; ANZULOVICH, AC

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2012 vol. 24 p. 859 - 867

0955-2863

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 RARá, RARâ and RXRâ 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 RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ A-deficient diet on the circadian expression of BMAL1, PER1 and retinoic acid receptors (RARs and RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ RXRâ 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 RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ A-deficient diet on the circadian expression of BMAL1, PER1 and retinoic acid receptors (RARs and RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ á, RARâ and RXRâ 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 RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ A-deficient diet on the circadian expression of BMAL1, PER1 and retinoic acid receptors (RARs and RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ â 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 RXRâ) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ maintained under 12h-light:12h-dark or 12h-dark:12h-dark during the last week of treatment. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ â) 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. RARá, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRâ á, RARâ, RXRâ, BMAL1 and PER1 transcript and protein levels were determined in hippocampus samples isolated every 4h in a 24h period. Regulatory regions of RARs and RXRââ 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 Adeficient 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.