EFFECTS OF PIOGLITAZONEVALPROIC ACID ON DAILY RHYTHMS OF LIPID PEROXIDATION AND ANTIOXIDANT ENZYMES IN AN AB(1-42) INDUCED RAT MODEL OF ALZHEIMER DISEASE.

CORTEZ M; CANGIANO B; ALBA R; DELGADO SM; ANZULOVICH AC; NAVIGATORE FONZO LS

MODALIDAD VIRTUAL

Congreso; XXXVI Congreso Anual de la SAN; 2021

Alzheimer's disease (AD) is a primary cause of dementia in the elderly. It is determined by the deposits of Aβwhich leads to memory impairment, oxidative stress associated to a deficientantioxidant defense system. AD patients also show alterations in their circadian rhythms. Numerous studieshave shown that Pioglitazone (Pio) possess antioxidant properties and Valproic Acid (VA)improved cognitive deficits in an experimental model of AD. Taking into account these observations,the objective of this study was to evaluate the effect of Pio/VA, on the 24h rhythms of lipidperoxidation, as well as on catalase (CAT) and glutathione peroxidase (GPx) expression and activityand Bdnf/TrkB expression in the hippocampus of Aβ-injected rats. Four-month-old males Holtzmanrats were divided into three groups defined as: 1) control 2) Aβ-injected 3) Aβ-injected treated withPio-VA. Rats were maintained under 12h-Light:12h-Dark conditions. Lipid peroxidation levels weredetermined by colorimetric assays and CAT and GPx enzymatic activities by kinetic assays. CAT, GPxand Bdnf/TrkB transcript levels were determined by RT-PCR in hippocampus samples isolated every 6h. We found that the treatment of Pio-VA reestablished rhythmicity of those temporal patterns. Thesefindings might constitute, at least in part, molecular and biochemical basis of restoration of circadianrhythmicity by the administration of Pio-VA in neurodegenerative disorders.