Chronobiology
Author: Ivanna Carla Castro Pascual | email: iccastro@email.unsl.edu.ar
Belen Cangiano 1°, Ivanna Castro-Pascual 1°, Mayra Cortez 1°, Carina Ledesma 1°, Cinthia Coria-Lucero 1°, Andrea Castro 1°, Ana Cecilia Anzulovich 1°, Silvia Delgado 1°, Lorena Navigatore-Fonzo 1°
1° Laboratorio de Cronobiologia-IMIBIO-CONICET-UNSL
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder. The accumulation of amyloid-? (A?) peptide in the brain is associated with cognitive déficits. Bcl-2 is the primary protein that inhibits cell apoptosis whereas Bax promotes apoptosis. Synthetic PPAR? agonists such 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 an intracerebroventricular injection of A?(1-42) modified the daily patterns of Bax and Bcl-2 expression in the rat hippocampus. Taking into account those observations, the objectives of this study were: first, to investigate the effects of pioglitazone-retinoic acid (Pio-RA) on the daily rhythms of Bax, Bcl-2 and Bmal1; second, to evaluate the effect of Pio-RA on cognitive performance. Four-month old males Holtzman rats were used in this study. Groups were defined as: 1) control 2) A?-injected 3) A?-injected treated with Pio-RA. Bax and Bcl-2 mRNA levels were determined by RT-PCR and clock protein levels were analyzed by immunoblotting in hippocampus samples isolated every 6h throughout a 24-h period. The cognitive function was evaluated by Novel Object Recognition test. We found that treatment of Pio-RA reestablished the daily rhythms of Bax, Bcl-2 and Bmal1 and improved cognitive disorders. These findings suggest that the administration of Pio-RA would be a novel therapeutic strategy for AD.