Neuromodulin expression varies throughout the day in the hippocampus and is modified by a vitamin A-free diet.

GOLINI RS; NAVIGATORE FONZO LS; STAGNITTA PV; DELGADO SM; ANZULOVICH AC

Potrero de los Funes, San Luis

Congreso; XXX Reunión Anual de la Soc. de Biologia de Cuyo; 2012

Neuromodulin (GAP), the pre-synaptic PKC substrate, is involved in synaptic plasticity. Previously, we reported that Neurogranin (RC3), the pos-synaptic substrate of PKC displays a circadian rhythm in the hippocampus, which was modified by the vitamin A deficiency. Retinoic acid, a vitamin A derivative, regulates phenomena related to cognitive function by activating nuclear receptors, RARs and RXRs. Our objectives were to investigate whether GAP-43 also displays a circadian expression pattern in the rat hippocampus and to evaluate the effect of a vitamin A-depleted diet on GAP43 temporal patterns. Holtzman rats received a diet containing 4000 IU of vitamin A/Kg diet (Control), or the same diet devoided of vitamin A (VitaminA-deficient, VAD, group), during 3 months. Rats were maintained under constant darkness conditions during 10 days before the experiment. GAP-43 and RORα mRNA levels were determined by RT-PCR and RARα, RXRß, BMAL1 and PER1 proteins by immunoblotting, in hippocampus samples isolated every 4 h during a 24h period. Regulatory region of GAP-43 gene was scanned for clock- and retinoic acid-responsive sites. E-box, RXRE, RARE and RORE sites were found. GAP-43 expression displays an endogenously-controlled daily variation in the rat hippocampus, which was modified in the VAD group; probably, by altering the circadian patterns of key clock and/or retinoic acid receptors proteins.