AGING MODIFIES TEMPORAL PATTERNS OF OXIDATIVE STRESS AND PROINFLAMMATORY MARKERS IN THE RAT PREFRONTAL CORTEX

PONCE IT; CORIA LUCERO, C; NAVIGATORE FONZO LS; DEVIA, C; FERNANDEZ G; KLUSCH, E; DELGADO SM; ANZULOVICH AC

MENDOZA

Congreso; XXXVI REUNION CIENTIFICA DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2018

Aging is often accompanied by a decline in cognitive function in conjunction with a variety of neurobiological changes, such as neuroinflammation and oxidative damage. The brain is vulnerable to oxidative damage because of its large amount of polyunsaturated fatty acids and relative deficiency in antioxidative defense mechanisms. Recent research has shown that the expression of proinflammatorycytokines increases with aging in brain. Besides cognitive deficit, older personsshow alterations in their circadian rhythms.The objective of this work was to investigate the consequences of aging on 24h patterns of oxidative stress parameters (TBARS and protein carbonyls)as well as TNFα, BMAL1 and RORα protein levels, in the rat prefrontal cortex (PFC). Holtzman rats from young (3-month-old) and aged (22-month-old) groups were maintained under constant darkness conditions, during 10 days before the experiment. Tissues samples were isolated every 6 h during a 24h period. TBAR?s levels were measured by a colorimetric assay and protein carbonyls by ELISA. Protein levels of TNFα, BMAL1 and RORα were determined by immunoblotting. As expected, we observed an increase in the protein carbonyls levels in the PFC ofaged rats. We also found that lipoperoxidation as well as protein levels of TNFα, BMAL1 and RORα follow a robust circadian rhythm in this tissue.Interestingly,aging abolishes the oscillation of endogenous circadian patterns oflipoperoxidation, TNFα, BMAL1 and RORα protein levels.These findings may constitute, at least in part, the molecular basis of the relationship between TNFmediated neuroinflammation and altered circadian rhythms of protein clock in aged individuals