DAILY RHYTHMS OF Aβ-DEGRADING ENZYMES IN THE RAT HIPPOCAMPUS. EFFECT OF AN I.C.V. INJECTION OF AMYLOID BETA PEPTIDE (1-42) AGGREGATES

CASTRO, ANDREA; CORIA-LUCERO, CINTHIA D.; LEDESMA CARINA; ANZULOVICH, ANA C.; NAVIGATORE FONZO LORENA

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

One of themain pathological features in the Alzheimer disease (AD) is the presence ofsenile plaques, primarily composed of Aβ peptide aggregates, in cortex and hippocampus.AD late onset, which constitutes 90% of cases, could be mainly attributable todeficiencies in the clearance of the Aß peptide.The objective of this work was to investigate the effectsof ani.c.v. injection of Aβ(1-42) aggregateson the 24hrhythms of Aβ-degrading enzymes as well as Aβ, BMAL1 andRORα protein levels, in the rat hippocampus. Four-month-old male Holtzman ratswere divided into two groups defined as: control (CO) and Aβ-injected (Aβ).Rats were maintained under12h-light:12h-dark conditions and received water andfood ad libitum. Tissues samples were isolated every 6 h during a 24h period.NEP, ECE and IDE mRNA levels were determined by RT-PCR and Aβ, BMAL1 and RORαprotein levels were analyzed by immunoblotting.Interestingly,we found thatexpression of Aβ-degrading enzymes varies on a daily basis in thehippocampus and that an i.c.v. injection of Aβ aggregates phase shifted dailyNEP and IDE expression and increased the mesor of ECE rhythms, as well as clockproteins (BMAL1 and RORα) daily rhythms. According to these results, we couldsuggest that the changes in the temporal patterns of enzymes involved in theclearance of Aβ, would precede the increase in the Aβ peptide levels and thedeterioration of the endogenous clock function, observed in the Alzheimer?sdisease