- EFFECT OF AN I.C.V. INJECTION OF AGREGATED BETA-AMYLOID (1-42) ON DAILY PROFILES OF Aβ-DEGRADING ENZYMES IN THE RAT HIPPOCAMPUS

CANGIANO B; CORTEZ M; SANCHEZ M; ALBA M; ANZULOVICH AC; DELGADO SM; NAVIGATORE FONZO LS

MENDOZA

Congreso; XL REUNION CIENTIFICA DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2022

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the most common form of irreversible dementia, amongthe elderly people. The accumulation of amyloid-β (Aβ) peptides in the brain of Alzheimer disease patients is associated tocognitive deficit, loss of memory and alterations in the circadian rhythms. Enzymes with Aβ-degrading activity include membersof the zinc metalloendopeptidase family. Among them, the ones with the most physiological relevance in the brain are endothelinconverting enzymes (ECE) and insulindegrading enzyme (IDE). Brain-derived neurotrophic factor (BDNF) and its receptor (TrkB),play an important role in the synaptic plasticity underlying memory and learning. Previously, we observed Aβ and BMAL1expression follow a daily rhythmic pattern in the prefrontal cortex of Aβ-injected rat. The objective of this work was to investigatethe effects of an i.c.v. injection of aggregated beta amyloid (1-42) on daily patterns of ECE and IDE expression, as well as onoscillating BDNF and TrkB mRNA levels, throughout a 24 h period, in the rat prefrontal cortex. Four-month-old males Holtzmanrats were divided into two groups defined as: control (CO) and Aβ-injected (Aβ) groups. Tissues samples were isolated every 6 hduring a 24h. IDE, ECE, BDNF and TrkB mRNA levels were determined by RT-PCR. We found that expression of Aβ-degradingenzymes and cognition-related factors varies on a daily basis in the prefrontal cortex and that an i.c.v. injection of Aβ aggregatesmodified these daily rhythms. Therefore, elevated levels of Aβ peptides could modify the temporal patterns of Aβ-degradingenzymes and consequently could affect the transcriptional activity of the endogenous cellular clock.