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 C; CAMPOS L; LEDEZMA C; DELGADO SM; ANZULOVICH A; NAVIGATORE FONZO L

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-γagonists have shown neuroprotective effects in neurodegenerative disorders. Previous studies indicate a role of retinoic acid incognitive activities and anti-amyloidogenic properties. Previously, we found that an intracerebroventricular (i.c.v) injection of Aβ(1-42) 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 ratTC; second, to evaluate the effect of the PPARγ agonist, pioglitazone, along to the RXR ligand, retinoic acid, on those temporalpatterns. 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, BMAL1andRORα proteins levels were determined by immunoblotting. To analyze the daily rhythmicity, 12 rats from each group were used. Thedata were analyzed by one-way ANOVA followed by the Tukey, a p