DAILY RC3 AND GAP43 EXPRESSION IS MODIFIED IN THE HIPPOCAMPUS FOLLOWING AN INTRACEREBROVENTRICULAR INJECTION OF AMYLOID BETA PEPTIDE

PIGNATARO, V; LEDEZMA, C; ANZULOVICH AC; NAVIGATORE FONZO LS

Congreso; Tercera Reunión Conjunta de Sociedades de Biología de la República Argentina; 2015

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. The accumulation of amyloid-β (Aβ) peptides in the brain is associated with cognitive deficits. Neurogranin (RC3) and neuromodulin (GAP43) are protein kinase C substrates that play an important role in the neuroplasticity mechanism underlying learning and memory and are expressed in the hippocampus. Besides the cognitive deficit, AD patients also show alterations in their circadian rhythms. Previously, we showed that injection of Aβ(1-42) phase shifted BDNF daily rhythms in rat Hippocampus. Continuing with that, the objective of this study was to investigate the effects of an i.c.v. injection of Aβ(1-42) peptide on RC3 and GAP43 expression as well as on Aβ protein levels, throughout a 24 h period, in rat hippocampus. Four-month-old male Holtzman rats divided into the control groups (CO) and Aβ-injected groups (Aβ) were maintained under 12h-light/12h-dark conditions. RC3 and GAP-43 mRNA levels were determined by RT-PCR and Aβ protein by immunoblotting, in hippocampus samples isolated every 4 h during a 24h period. Regulatory regions of RC3 and GAP43 were scanned for E-box sites. We found E-box sites on regulatory regions of RC3 and GAP43 genes and observed daily rhythms of RC3 expression in the rat hippocampus. Even though GAP43 expresion varies significantly throughout the day, its temporal pattern is not adjusted to a cosine curve. The i.c.v. injection of Aβ (1-42) increased Aβ content, phase shifted RC3 daily rhythms and abolished the GAP43 mRNA levels variation. Elevated Aβ peptide levels might modify the temporal patterns of cognition-related factors, probably by afecting the endogenous clock factors rhythms in the hippocampus.