EFFECT OF A PPARGAMA SYNTHETIC AGONIST ASSOCIATED WITH RETINOIC ACID ON THE 24-HOUR RHYTHMS OF BMAL1 AND RORα PROTEINS IN AN EXPERIMENTAL MODEL OF ALZHEIMER DISEASE

CORIA LUCERO CINTHIA; LEDESMA CARINA; ANZULOVICH, ANA C.; CAMPOS LUDMILA; DELGADO, SILVIA M.; NAVIGATORE FONZO LORENA

San Luis

Congreso; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2019

Alzheimer´s disease (AD) pathogenesis is associated to cognitive deficit and alterations in the circadian rhythms. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. Previous studies indicate a role of retinoic acid in cognitive activities and anti-amyloidogenic properties. Previously, we found that an i.c.v. injection of Aβ(1-42) modified the daily rhythms of Aβ and BMAL1in the rat temporal cortex (TC). Continuing with that study, the objectives of this study were: first, to analyze the effect of an i.c.v. injection of Aβ(1-42) peptide on the 24h rhythms of RORα protein levels in the rat TC; second, to evaluate the effect of the PPARγ agonist, pioglitazone, along to the RXR ligand, retinoic acid, on those temporal patterns. Groups were defined as: 1) control 2) Aβ-injected 3) Aβ-injected treated with Pio-RA. TC samples were isolated every 4 h during a 24h period. Aβ, BMAL1and RORα proteins levels were determined by immunoblotting. We found that injection of Aβ(1-42) modified the daily rhythms of RORα protein level in the rat TC. The treatment of Pio-RA reestablished the daily rhythms of Aβ, BMAL1 and RORα protein levels. These findings would emphasize the importance of Pio-RA in the modulation of daily rhythmicity of clock gene in AD.