EFFECT OF I.C.V. AGREGATED β-AMYLOID (1-42) ON DAILY PATTERNS OF COGNITION-RELATED FACTORS IN THE RAT TEMPORAL CORTEX

CORIA LUCERO, C; GOLINI RS; ANZULOVICH AC; NAVIGATORE FONZO LS

TUCUMAN

Congreso; 3ER REUNION CONJUNTA DE LAS SOCIEDADES DE BIOLOGIA DE LA REP. ARGENTINA; 2015

SOCIEDADES DE BIOLOGIA

Alzheimer?s disease (AD) is the most common form of dementia. Elevated levels of β-amyloid peptide (Aβ) in different areas of the Central Nervous System (CNS), including cortex, and progressive cognitive impairment, are characteristics of AD. Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, (TrkB), play a central role in the CNS by regulating synaptic plasticity and memory. TrkB and BDNF signaling are impaired in AD. Besides the cognitive deficit, AD patients also show alterations in their circadian rhythms. Previously, we showed that aging abolished Trkb circadian rhythms and phase shifted BDNF endogenous rhythms in the temporal cortex. Continuing with that study, our objective was to investigate the effects of an i.c.v. injection of Aβ(1-42) peptide on the 24h rhythms of BDNF and TrkB expression, as well as on BMAL1 and Aβ protein levels, in the rat temporal cortex. Four-month-old males Holtzman rats were used in this study. Groups were defined as: control (CO) and Aβ-injected (Aβ). Rats were maintained under 12h-light:12h-dark throughout the entire experimental period. Total RNA was extracted using the Trizol reagent from temporal cortex samples isolated every 6h throughout a 24h period. Transcript levels of BDNF and TrkB were determined by RT-PCR and normalized to 28S as endogenous control. Protein levels were analyzed by Western blots. We found i.c.v. injection of Aβ(1-42) increased Aβ peptide content and phase shifted daily variation of BDNF and TrkB expression in the rat temporal cortex, probably, by altering the daily patterns of clock activator (BMAL1) as a result of Aβ peptide accumulation. These results may constitute, at least in part, a molecular and cronobiological basis for deficits in temporal organization of temporal cortex-related cognitive functions in AD.