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

Abstract

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

Evaluating Circadian Dysfunction in Mouse Models of Alzheimer’s Disease: Where Do We Stand?

“…More detailed studies which incorporate pathology assessments are needed. Injection of Aβ peptide into the brain of wild type mice has also been used to model AD, and has been reported to lengthen period and blunt clock gene rhythms in the SCN (Navigatore-Fonzo et al, 2017), and to alter expression patterns of Apoe and other mRNAs in the hippocampus (Wang et al, 2016), though this model is not widely used.…”

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

“…SIRT1 activation by resveratrol may target a myriad of neuronal injury and neurodegeneration paradigms (Herskovits and Guarente, 2014). Of these, both Aβ and Pb are able to potentiate formation of oxidation products that will lead to neurotoxicity and DNA damage (Sanders T. et al, 2015; Navigatore-Fonzo et al, 2017). It is proposed that resveratrol can attenuate Aβ-induced neurotoxicity through activating SIRT1 signaling and autophagy (Deng and Mi, 2016; Wang et al, 2017).…”

An intracerebroventricular injection of amyloid-beta peptide (1–42) aggregates modifies daily temporal organization of clock factors expression, protein carbonyls and antioxidant enzymes in the rat hippocampus

“…Interestingly, we found, for the first time in our knowledge, that an i.c.v injection of Aβ aggregates caused a phase shift and increase the rhythm's amplitude of protein oxidation levels in comparison to controls (Figure 1, Table 1). Previously, we found that an injection of Aß aggregates caused a phase shift in daily oscillations of lipoperoxidation levels (acrophase: 19:48±00:54 vs 10:16±01:42) and increased their rhythm's amplitude (Navigatore Fonzo et al, 2017). Our previous results showed that Aβ proteins display a daily oscillation profile in the hippocampus of Aβ-injected rats, with maximal Aβ levels occurring at ZT 07:09±00:17 (Navigatore Fonzo et al, 2017).…”

“…Previously, we found that an injection of Aß aggregates caused a phase shift in daily oscillations of lipoperoxidation levels (acrophase: 19:48±00:54 vs 10:16±01:42) and increased their rhythm's amplitude (Navigatore Fonzo et al, 2017). Our previous results showed that Aβ proteins display a daily oscillation profile in the hippocampus of Aβ-injected rats, with maximal Aβ levels occurring at ZT 07:09±00:17 (Navigatore Fonzo et al, 2017). As expected, peaks of lipid peroxides and protein oxidation levels occur at the middle and at the end of the night, respectively, following Aβ expression rhythm's acrophase (ZT 07:09±00:17) in the hippocampus of Aβ-injected rats, in the context of reactive homeostasis.…”