Effects of Pioglitazone-Retinoic Acid on Daily Rhythms of Oxidative Stress Parameters in an Experimental Model of Alzheimer Disease

LEDEZMA, C; CORIA LUCERO, C; CASTRO A; DELGADO SM; ANZULOVICH AC; NAVIGATORE FONZO LS

Córdoba

Congreso; XXXIII Congreso de la SAN; 2018

Alzheimer?s disease (AD) is the main cause of dementia in the elderly. The pathological hallmarks of AD include senile plaques of amyloid-b (Ab) aggregates and neurofibrillary tangles in brain. Elevated levels of Ab causes an increase in intracellular reactive oxygen species associated to a deficient antioxidant defense system. The objectives of this study were: first, to analyze the effect of an i.c.v. injection of Ab (1-42) on the 24-hr rhythms of oxidative stress parameters in the rat prefrontal cortex (PC); second, to evaluate the effect of pioglitazone-retinoic acid (Pio-RA) on those temporal patterns. Four-month old males Holtzman rats were used in this study. Groups were defined as: (a) control, (b) Ab-injected, and (c) Ab-injected treated with Pio-RA. PC samples were isolated every 4 hr during a 24-hr period. Lipid peroxidation and protein carbonyls levels were determined by colorimetric assays and ELISA, respectively. CAT and GPx enzymatic activities were determined by kinetic assays and Ab, BMAL1 proteins levels by immunoblotting. We found that injection of Ab(1-42) modified the daily rhythms of lipid peroxidation, protein carbonyls, CAT and GPx enzymatic activities, Ab and BMAL1 protein levels in the rat PC. The treatment of Pio-RA reestablished rhythmicity of those temporal patterns. These findings might constitute, at least in part, molecular and biochemical basis of restoration of circadian rhythmicity by the administration of Pio-AR in neurodegenerative disorders.