EFFECTS OF PIOGLITAZONE-RETINOIC ACID ON DAILY RHYTHMS OF RC3 AND GAP43 IN THE HIPPOCAMPUS OF Aβ-INJECTED RAT

CANGIANO BELEN; CORTEZ MAYRA; GOLINI R; CASTRO ANDREA; CORIA LUCERO; LEDEZMA, CARINA; DELGADO, SILVIA; ANZULOVICH, ANA C.; NAVIGATORE FONZO LORENA

Congreso; XXXVI Reunion Anual de la Sociedad Argentina de Investigación en Neurociencias; 2021

Alzheimer?s disease (AD) is the most frequent form of dementia in older people. Elevated levels of beta-amyloid(Aβ)peptide causes oxidative stress which lead to a gradual impairment of memory. Neurogranin(RC3) and neuromodulin(GAP43) play an important role in the learning and memory. Pioglitazone(Pio) and retinoic acid (RA) have antioxidantproperties. In addition, pioglitazone improved cognitive performance in Alzheimer's patients. Previously, we havedemonstrated that an icv injection of Aβ(1-42) modified the daily rhythms of oxidative stress parameters and cognitionrelatedfactorsinthehippocampusofrat.Continuingwiththatstudy,theobjectiveofthisworkwastoevaluatetheeffectofPio/RA on RC3 and GAP43 expression as well as on Aβ protein levels, lipid peroxidation and protein carbonylsthroughout a 24 h period, in the hippocampus Aβ-injected rat. Four-month-old male Holtzman rats divided into the groupscontrol, Aβ-injected and Aβ-injected treated with Pio/RA were maintained under 12h-light12h-dark conditions. RC3 andGAP-43 mRNA levels were determined by RT-PCR. Lipid peroxidation and protein carbonyls levels were determined bycolorimetric assays. Aβ protein levels were analyzed by immunoblotting. We found that Pio/RA reestablished rhythmicityof those temporal patterns. These findings might constitute, at least in part, molecular and biochemical basis of restorationof circadian rhythmicity by the administration of Pio/RA in neurodegenerative disorders.