Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer?s disease

ANZULOVICH A; NAVIGATORE FONZO, LORENA; GARRAZA M

BRAIN RESEARCH REVIEWS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 1660 p. 27 - 35

0165-0173

The accumulation of amyloid-b (Ab) peptides in the brain of Alzheimer disease patients is associated tocognitive deficit, increased oxidative stress, and alterations in the circadian rhythms. Brain-derived neurotrophicfactor (BDNF) and Neurogranin (RC3), play an important role in the synaptic plasticity underlyingmemory and learning. Previously, we observed BDNF and RC3 expression follow a daily rhythmicpattern in the hippocampus of young rats. The objective of this study was to investigate the effects ofan intracerebroventricular (i.c.v) injection of aggregated Ab peptide (1?42) on temporal patterns ofApoE protein, Bdnf and Rc3 mRNA, lipid peroxidation (LPO) and reduced glutathione (GSH) levels, inthe rat hippocampus. We observed an i.c.v. injection of Ab aggregates phase shifts daily BDNF and RC3expression as well as LPO and decreased the mesor of GSH rhythms. ApoE protein levels vary rhythmicallythroughout the day. ApoE levels increase at ZT 03:39 ± 00:22 in the hippocampus of control ratsand at ZT 06:30 ± 00:28 in the treated animals. Thus, elevated levels of Ab aggregates, characteristic ofAD, altered temporal patterns of cognition related-factors, probably, as a consequence of changes inthe daily variation of ApoE-mediated Ab aggregates clearance as well as in the 24 h rhythms of the cellularredox state.