EFFECT OF AN I.C.V. INJECTION OF AMYLOID BETA PEPTIDE (1-42) ON

NAVIGATORE FONZO, L; DEYURKA NICOLAS; GARRAZA MARISA; ANZULOVICH, AC

Congreso; XXXIII Reunión Anual de la Sociedad de Biologia de Cuyo,; 2015

Alzheimer´s disease (AD) is a neurodegenerative disorder that leads to memory loss, dementia, and death.  Accumulation of Aâ 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 Aâ(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 an i.c.v. injection of Aâ(1-42) peptide on temporal patterns of lipid peroxidation and glutathione (GSH) levels, as well as on Aâ protein levels, in the rat hippocampus. Four-month-old males Holtzman rats were divided into two groups defined as: control (CO) and Aâ-injected (Aâ). Rats were maintained under 12h-light:12h-dark conditions and received water and food ad libitum. Hippocampus samples were isolated every 4 h during a 24h period. Lipid peroxidation and GSH levels were determined by colorimetric assays. Aâ protein levels were analyzed by immunoblotting. We found that i.c.v. injection of Aâ(1-42) increased Aâ peptide content in the hippocampus and phase shifted Aâ, lipid peroxidation and GSH daily rhythms. These changes follow the previously observed changes in daily patterns of antioxidant enzymes activity. Thus, elevated Aâ peptide levels alter temporal patterns of oxidative stress-related parameters and, consequently, would negatively affect cellular clock activity in the hippocampus.