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

ANZULOVICH AC; NAVIGATORE FONZO LS; LEDEZMA, C; DELGADO SM; CORIA LUCERO, C; CAMPOS LE

SAN LUIS

Congreso; XXXVII REUNION CIENTIFICA DE LA SOCIEDAD DE BIOLOGIA 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 intracerebroventricular (i.c.v) injection of Aβ(142) modified the daily rhythms of Aβ and BMAL1 in 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 (saline solution) 2) Aβ-injected (Aβ aggregates-10 µg) 3) Aβ-injected treated with PioRA (Aβ aggregates-10 µg) and (Pio 10mg/kg, ip)/AR (1mg/kg, ip) by 15 days. Rats were injected into the lateral ventricle (coordinates: AP:-1 mm, L:1.5 mm, and DV:-3.5 mm). TC samples were isolated every 4 h during a 24h period. Aβ, BMAL1and RORα proteins levels were determined by immunoblotting. To analyze the daily rhythmicity, 12 rats from each group were used. The data were analyzed by one-way ANOVA followed by the Tukey, a p