Circadian expression of RARs and RXRs is modified in the hippocampus of vitamin-A deficient rats

NAVIGATORE FONZO, LS; GOLINI R; DELGADO S.M; BONOMI M.R; GIMENEZ, MS; ANZULOVICH, AC

Tucuman

Congreso; XLV Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2009

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

An endogenous time-keeping mechanism controls circadian biological rhythms in mammals. Previously, we showed clock and clock-controlled genes display a daily rhythmicity in the rat hippocampus. RAR and RXR nuclear receptors have been detected in the same area. Our objectives were to investigate whether RARá, RARâ and RXRâ exhibit a circadian variation in the rat hippocampus and whether vitamin A deficiency (VAD) modifies their daily expression. Twenty one-d old Holtzman rats were assigned to either a vitamin A-free diet (vitamin A-deficient group) or the same diet containing 4000 IU of vitamin A/Kg diet (control group) during 3 months. Half of the animals in each group were maintained under 12h-L:12h-D or 12h-D:12h-D during the last week. Total RNA was extracted using the Trizol reagent from hippocampus samples isolated every 4h. RARá, RARâ and RXRâ transcript levels were determined by RT-PCR. Protein levels by Western blots. Regulatory regions of RARs and RXRâ genes were scanned for clock-responsive sites using MatInspector (www.genomatix.de). 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. VAD modified the daily rhythmicity of RARá and RXRâ probably, by modifying BMAL1 and PER1 oscillation. (Supported by NIH Grant R01-TW006974 funded by the FIC, USA).