Effect of a PPARγ 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 C; LEDEZMA C; ANZULOVICH AC; CAMPOS LE; DELGADO S; NAVIGATORE FONZO L

San Luis capital

Congreso; XXXVII Reunión Científica Annual de la Sociedad de Biología de Cuyo (SBC); 2019

Sociedad de Biología de Cuyo

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 thisstudy 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 15days. 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 wereanalyzed by one-way ANOVA followed by the Tukey, a p