EFFECTS OF EXPERIMENTAL INTRACEREBROVENTRICULAR INJECTION OF AMYLOID BETA PEPTIDE (1-42) ON THE DAILY Bax AND Bcl-2 EXPRESSION IN THE RAT HIPPOCAMPUS

ALFARO MAURO ; CORIA LUCERO; LEDESMA CARINA; CASTRO ANDREA; MENDOZA GISELA; ANZULOVICH AC.; NAVIGATORE FONZO LORENA

Congreso; XXXIX Reunión Científica de la SBCuyo; 2021

Alzheimer disease (AD) is a neurodegenerative disorder marked bycognitive and behavioral impairment. The accumulation of amyloid-β (Aβ)peptides in the brain are believed to be associated with perturbations ofsynaptic function leading to cognitive 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'sdisease (AD).  Besides the cognitivedeficit, AD patients also show alterations in their circadian rhythms.  The objective of this study was to investigatethe effects of an intracerebroventricular (i.c.v) injection of amyloid betapeptide (1-42) on daily patterns of Bax and Bcl-2 expression, as well as ofclock proteins in the hippocampus and on temporal profiles of cognitiveperformance of four-month-old males Holtzman rats. Groups were defined as:control (CO) and Aβ-injected (Aβ). Rats were maintained under12h-light:12h-dark conditions and received food and water ad libitum throughoutthe entire experimental. Daily rhythms of Bax and Bcl-2 expression wereanalyzed by RT- PCR and protein levels by Western blots, in hippocampus samplesisolated every 4 h during a 24h period. Regulatory regions of Bax and Bcl-2were scanned for E-box sites. The Novel Object Recognition (NOR) test was usedto evaluate cognition, particularly recognition memory. We found E-box sites onregulatory regions of Bax and Bcl-2 genes, which display a daily oscillation ofexpression 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 thegroup injected with Aβ explored the novel object for less time compared to thecontrol group, during the day and night periods. Thus, elevated Aβ peptidelevels might affected the temporal patterns of cognitive function and apoptoticgenes, probably by altering daily rhythms of clock proteins.