EFFECT OF A PPARG SYNTHETIC AGONIST ASSOCIATED WITH VALPROIC ACID ON THE 24-HOUR RHYTHMS OF INSULIN-DEGRADING ENZYME IN AN EXPERIMENTAL MODEL OF ALZHEIMER S DISEASE

SANCHEZ M; CANGIANO B; CORTEZ M; GOLINI RS; ALBA R; GARRAZA M; ANZULOVICH AC; NAVIGATORE FONZO LS

MENDOZA

Congreso; SBCuyo 2022; 2022

Alzheimer disease (AD) is the most common form of age-related neurodegenerative disorder. Numerous studies haveshown that an imbalance between the production and clearance of amyloid- the-degrading enzyme (IDE) plays a crucial role in the clearance of Alzheimer samyloid- Numerous studies have shown that pioglitazone (Pio), a PPARpropertiesand improves cognitive deficits in AD. Valproic acid (VPA), a multifunctional drug, plays important roles inpromoting the release of neurotrophic factor and improving memory deficits. In addition, evidence shows that themolecular clock function depends on the cellular redox state. Previously, we found that the treatment of Pio/VPAreestablished rhythmicity of oxidative stress parameters in the hippocampus. Taking into account these observations, theobjective of this study was to evaluate the effect of Pio/VPA on the 24- , IDE, BDNF and its receptor in-injected rats. Four-month-old male Holtzman rats were divided into three groups: (1) control, (2)-injected, and ( -injected treated with Pio/VPA. Rats were maintained under 12 h-light:12 h-dark conditions andreceived water and food ad libitum. Hippocampal samples were obtained every 6 h during a 24-h period. Transcript levelsof insulin-degrading enzyme and cognition-related factors were determined by RT- by-42) phase-Pio/VPA reestablished rhythmicity of those temporal patterns. Thus, combination therapy with pioglitazone and valproicacid ameliorates pathologic changes observed in an experimental model of AD and might represent a potential treatmentapproach for AD.