EFFECTS OF PIOGLITAZONE-RETINOIC ACIDON DAILY RHYTHMS OF OXIDATIVE STRESS PARAMETERS IN AN EXPERIMENTAL MODEL OF ALZHEIMER DISEASE

CASTRO, ANDREA; CORIA-LUCERO, CINTHIA D.; NAVIGATORE FONZO LORENA; LEDESMA CARINA; ANZULOVICH, ANA CECILIA

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

Alzheimer´s disease (AD) is the main cause of dementia in the elderly.Thepathological hallmarks of AD include senile plaques of amyloid-β(Aβ) aggregatesand neurofibrillary tangles in brain.Elevated levels of Aβ causes an increasein intracellular reactive oxygen species associated to a deficient antioxidantdefense system. The objectives of this study were: first, to analyze the effectof an i.c.v. injection of Aβ(1-42) on the 24h rhythms of oxidative stressparameters in the rat prefrontal cortex(PC); second, to evaluate the effect ofpioglitazone-retinoic acid (Pio-RA) on those temporal patterns. Four-month oldmales Holtzman rats were used in this study. Groups were defined as: 1) control2) Aβ-injected 3) Aβ-injected treated with Pio-RA. PC samples were isolatedevery 4 h during a 24h period. Lipid peroxidationand protein carbonyls levels weredetermined by colorimetric assays and ELISA,respectively. CAT and GPx enzymatic activities were determined by kinetic assays andAβ, BMAL1 proteins levels by immunoblotting. We found that injection of Aβ(1-42)modifiedthe daily rhythms of lipid peroxidation, protein carbonyls, CAT and GPxenzymatic activities, Aβ and BMAL1 protein levels in the rat PC. The treatmentof Pio-RA reestablished rhythmicity of those temporal patterns. These findingsmight constitute, at least in part, molecular and biochemical basis ofrestoration of circadian rhythmicity by the administration of Pio-ARinneurodegenerative disorders.