EFFECT OF A PPARg; SYNTHETIC AGONIST ASSOCIATED WITH RETINOIC ACID ON DAILY RHYTHMS OF BAX AND BCL-2 IN AN EXPERIMENTAL MODEL OF ALZHEIMER DISEASE

CANGIANO BELEN; CASTRO PASCUAL IVANA ; CORTEZ MAYRA; LEDESMA CARINA; CORIA LUCERO CINTHIA; CASTRO ANDREA; ANZULOVICH AC.; DELGADO S.M; NAVIGATORE FONZO LORENA

Congreso; XXXVII Reunión Anual de la SAN; 2022

SOciedad Argentina de Neurociencias

Alzheimer´s disease (AD) is an irreversible neurodegenerative disorder. The accumulation ofamyloid-β (Aβ) peptide in the brain is associated with cognitive déficits. Bcl-2 is the primaryprotein that inhibits cell apoptosis whereas Bax promotes apoptosis. Synthetic PPARγ agonistssuch as pioglitazone have been shown to improve cognitive performance in patients with AD.Previous studies indicate that retinoic acid rescues memory déficits. Previously, we found that anintracerebroventricular injection of Aβ(1-42) modified the daily patterns of Bax and Bcl-2expression in the rat hippocampus. Taking into account those observations, the objectives of thisstudy were: first, to investigate the effects of pioglitazone-retinoic acid (Pio-RA) on the dailyrhythms of Bax, Bcl-2 and Bmal1; second, to evaluate the effect of Pio-RA on cognitiveperformance. Four-month old males Holtzman rats were used in this study. Groups were definedas: 1) control 2) Aβ-injected 3) Aβ-injected treated with Pio-RA. Bax and Bcl-2 mRNA levels were determined by RT-PCR and clock protein levels were analyzed by immunoblotting inhippocampus samples isolated every 6h throughout a 24-h period. The cognitive function wasevaluated by Novel Object Recognition test. We found that treatment of Pio-RA reestablished thedaily rhythms of Bax, Bcl-2 and Bmal1 and improved cognitive disorders. These findings suggestthat the administration of Pio-RA would be a novel therapeutic strategy for Alzheimer´s disease