Intracerebroventricular injection of beta amyloid peptide (1-42) modifies the temporal organization of antioxidant defenses and oxidative stress in the prefrontal cortex.

RAMIREZ D; LEDEZMA C; DELGADO S; CORIA-LUCERO C; DELSOUC M; CASAIS M; DELLA VEDOVA M; ANZULOVICH A; NAVIGATORE FONZO L

Las Vegas

Congreso; Society for Redox Biology and Medicine's 26th Annual Conference; 2019

Accumulation of amyloid peptides in the brain plays a key role in the pathogenesis of Alzheimer´s disease (AD). Aggregated beta-amyloid (Aβ) peptide increases intracellular reactive oxygen species associated with a deficient antioxidant defense system. The prefrontal cortex plays a key role in memory and learning and is especially susceptible to oxidative stress. The objective of this work was to investigate the effects of an intracerebroventricular (i.c.v.) injection of Aβ (1-42) on 24h patterns of oxidative stress parameters and antioxidant defenses in the rat prefrontal cortex. Four-month-old male Holtzman rats were divided into two groups defined as control (CO) and Aβ injected (Aβ). Rats were maintained under12h-light:12h-dark conditions and received water and food ad libitum. Tissues samples were isolated every 6 h during a 24h period. Interestingly, we found that an i.c.v. injection of Aβ(1-42) increased lipid peroxidation, reduced total antioxidant capacity level, phase-shifted the daily peak of reduced glutathione, and had a differential effect on the oscillating catalase and glutathione peroxidase specific activity. Thus, elevated levels of Aβ aggregates-a pathogenic hallmark of AD caused altered temporal patterns of the cellular redox state in the prefrontal cortex rat. These findings might contribute, at least in part, to the understanding of the molecular and biochemical basis of redox changes caused by circadian rhythms alterations observed in AD patients.