Daily expression of Rev-Erba and Rora nuclear receptors is modified in the hippocampus of vitamin A-deficient rats.

NAVIGATORE FONZO LS; RAGUSSA V; DELGADO SM; ANZULOVICH AC

Huerta Grande, Cordoba

Congreso; I IRCN de la Sociedad Argentina de Investigación en Neurociencias y de la TAN; 2009

SAN

The REV-ERB/ROR orphan NR subfamily regulates the expression of core clock genes and contributes to the robustness of the clock mechanism. Retinoic acid receptors are involved in the resetting of peripheral clocks and RARá and RXRâ nuclear receptors have been detected in the rat hippocampus. The objectives of this study were to investigate whether Rev-Erbâ and Rorá displayed a circadian expression pattern in the rat hippocampus, and evaluate to which extent vitamin A deficiency could modify their daily oscillation by modifying RAR and/or RXR expression. Holtzman rats weaned at 21 d of age were immediately assigned to either the experimental diet, devoid of vitamin A (vitamin A-deficient group) or the same diet containing 4000 IU of vitamin A/Kg diet (control group) during 3 months. Hippocampus samples were taken every 4 h from control and vitamin A-deficient rats. Total RNA was extracted using the Trizol reagent and following manufacturer?s instructions. Transcript levels of Rev-Erbâ and Rorá were determined by RT-PCR. RARá and RXRâ mRNA levels were quantified by Real-time PCR. Protein levels were determined by immunoblotting. We found Rev-Erbâ and Rorá expression display a daily rhythmicity in the hippocampus of control rats. RXRâ transcript levels were significantly lower in the vitamin A-deficient rats compared to controls. Daily rhythms of mRNA and protein expression of Rev-Erbâ, Rorá and, consequently, Bmal1, were phase shifted in the vitamin A-deficient group. Thus, vitamin A deficiency modifies the circadian expression of core clock components in the hippocampus, probably, by reducing the availability of retinoid nuclear receptors such as RXRâ and phase shifting Rev-Erbâ/Rorá expression.