Daily Rhythms of Ab-Degrading Enzymes in the Rat Hippocampus. Effect of an i.c.v. Injection of Amyloid Beta Peptide (1-42) Aggregates

CASTRO A; CORIA LUCERO, C; LEDEZMA, C; ANZULOVICH AC; NAVIGATORE FONZO LS

Córdoba

Congreso; XXXIII Congreso de la SAN; 2018

One of the main pathological features in the Alzheimer disease (AD) is the presence of senile plaques, primarily composed of Ab peptide aggregates, in cortex and hippocampus. AD late onset, which constitutes 90% of cases, could be mainly attributable to deficiencies in the clearance of the Aß peptide. The objective of this work was to investigate the effects of an i.c.v. injection of Ab (1-42) aggregates on the 24-hr rhythms of Ab-degrading enzymes as well as Ab, BMAL1 and RORa protein levels, in the rat hippocampus. Four-month-old male Holtzman rats were divided into two groups defined as: control (CO) and Ab-injected (Ab). Rats were maintained under 12-hr light:12-hr dark conditions and received water and food ad libitum. Tissues samples were isolated every 6 hr during a 24-hr period. NEP, ECE, and IDE mRNA levels were determined by RT-PCR and Ab, BMAL1, and RORa protein levels were analyzed by immunoblotting. Interestingly, we found that expression of Ab-degrading enzymes varies on a daily basis in the hippocampus and that an i.c.v. injection of Ab aggregates phase shifted daily NEP and IDE expression and increased the mesor of ECE rhythms, as well as clock proteins (BMAL1 and RORa) daily rhythms. According to these results, we could suggest that the changes in the temporal patterns of enzymes involved in the clearance of Ab, would precede the increase in the Ab peptide levels and the deterioration of the endogenous clock function, observed in the Alzheimer?s disease.