EFFECTS OF EXPERIMENTAL INTRACEREBRO- VENTRICULAR INJECTION OF AMYLOID BETA PEPTIDE (1-42) ON THE DAILY BAX AND BCL-2 EXPRESSION IN THE RAT HIPPOCAMPUS

ALFARO, M; CORIA LUCERO, C; LEDEZMA, C; CASTRO A; MENDOZA G; ANZULOVICH AC; NAVIGATORE FONZO LS

MODALIDAD VIRTUAL

Congreso; XXXIX REUNION CIENTIFICA DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2021

Alzheimer disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. The accumulationsof amyloid-β (Aβ) peptides in the brain are believed to be associated with perturbations of synaptic function leading tocognitive déficits. The proto-oncogene Bax (Bcl-2-associated X protein) and related protein Bcl-2 (B-cell chroniclymphocytic leukemia/lymphoma-2) genes are triggers of apoptosis in Alzheimer's disease (AD). Besides the cognitivedeficit, AD patients also show alterations in their circadian rhythms. The objective of this study was to investigate the effectsof an intracerebroventricular (i.c.v) injection of amyloid beta peptide (1-42) on daily patterns of Bax and Bcl-2 expression,as well as of clock proteins in the hippocampus and on temporal profiles of cognitive performance of four-month-old malesHoltzman rats. Groups were defined as: control (CO) and Aβ-injected (Aβ). Rats were maintained under 12h-light:12h-darkconditions and received food and water ad libitum throughout the entire experimental. Daily rhythms of Bax and Bcl-2expression were analyzed by RT- PCR and protein levels by Western blots, in hippocampus samples isolated every 4 h duringa 24h period. Regulatory regions of Bax and Bcl-2 were scanned for E-box sites. The Novel Object Recognition (NOR) testwas used to evaluate cognition, particularly recognition memory. We found E-box sites on regulatory regions of Bax andBcl-2 genes, which display a daily oscillation of expression in the rat hippocampus. The i.c.v. injection of Aβ (1-42) modifieddaily variation of Bax and Bcl-2, and clock proteins. It was observed that the group injected with Aβ explored the novelobject for less time compared to the control group, during the day and night periods. Thus, elevated Aβ peptide levels mightaffected the temporal patterns of cognitive function and apoptotic genes, probably by altering daily rhythms of clock proteins.