Effect of i.c.v aggregated betha-amyloid (1-42) on the 24h rhythms of oxidative and antioxidative parameters in the prefrontal and temporal cortex and hippocampus of rats

CORIA-LUCERO, CINTHIA D.; LEDESMA CARINA; GOLINI REBECA; DEYURKA NICOLAS; DELLA VEDOBA CECILIA; RAMIREZ DARIO; DELGADO, SM; ANZULOVICH, ANA CECILIA; NAVIGATORE FONZO, LORENA

BUENOS AIRES

Congreso; II FEDERATIONOF LATIN AMERICANAND CARIBBEAN NEUROSCIENCE SOCIETIES; 2016

FALAM

Alzheimer´s disease (AD), is a neurodegenerative disorder that affects elderly people. The accumulation of amyloid peptides in the brain plays a key role in the pathogenesis of AD. Thus, elevated levels of beta peptide causes an increase in intracellular reactive oxygen species (ROS) and free radicals associated to a deficient antioxidant defense system. Besides oxidative stress and cognitive deficit, AD patients show alterations in their circadian rhythms. Previously, we showed that injection of Abeta(1-42) phase shifts CAT and GPx daily rhythms in the rat hippocampus. Continuing with that study, the objective of this work was to investigate the effects of i.c.v. aggregated betha-amyloid (1-42) on temporal patterns of oxidative stress, as well as on AB and BMAL1 protein levels, in the rat cortex and hippocampus. Four-month-old males Holtzman rats were divided into two groups defined as: control (CO) and Aβ-injected (AB). Rats were maintained under 12h-light:12h-dark conditions and received water and food ad libitum. Tissues samples were isolated every 4 h during a 24h period. Lipid peroxidation and GSH levels were determined by colorimetric assays and CAT enzymatic activity by kinetic assays and protein carbonyls by ELISA. Transcript levels of CAT and GPx were determined by RT-PCR and protein levels by Western blots. We found that i.c.v. injection of Aβ(1-42) phase shifted lipid peroxidation, CAT activity, GPx mRNA levels and protein carbonyls daily rhythms in cortex and hippocampus, as well as phase shifted AB and BMAL1 protein in these brain areas. Thus, beta peptide levels might modify the temporal patterns of oxidative and antioxidative parameters, probably, by affecting the endogenous clock factors rhythms in the hippocampus.