| Texto completo | |
| Autor(es): |
Kincheski, Grasielle C.
;
Valentim, Isabela S.
;
Clarke, Julia R.
;
Cozachenco, Danielle
;
Castelo-Branco, Morgana T. L.
;
Ramos-Lobo, Angela M.
;
Rumjanek, Vivian M. B. D.
;
Donato, Jr., Jose
;
De Felice, Fernanda G.
;
Ferreira, Sergio T.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BRAIN BEHAVIOR AND IMMUNITY; v. 64, p. 140-151, AUG 2017. |
| Citações Web of Science: | 31 |
| Resumo | |
It is increasingly recognized that sleep disturbances and Alzheimer's disease (AD) share a bidirectional relationship. AD patients exhibit sleep problems and alterations in the regulation of circadian rhythms; conversely, poor quality of sleep increases the risk of development of AD. The aim of the current study was to determine whether chronic sleep restriction potentiates the brain impact of amyloid-beta oligomers (ABOs), toxins that build up in AD brains and are thought to underlie synapse damage and memory impairment. We further investigated whether alterations in levels of pro-inflammatory mediators could play a role in memory impairment in sleep-restricted mice. We found that a single intracerebroventricular (i.c.v.) infusion of A beta Os disturbed sleep pattern in mice. Conversely, chronically sleep-restricted mice exhibited higher brain expression of pro-inflammatory mediators, reductions in levels of pre- and post-synaptic marker proteins, and exhibited increased susceptibility to the impact of i.c.v. infusion of a sub-toxic dose of ABOs (1 pmol) on performance in the novel object recognition memory task. Sleep-restricted mice further exhibited an increase in brain TNF-alpha levels in response to A beta Os. Interestingly, memory impairment in sleep-restricted A beta O-infused mice was prevented by treatment with the TNF-alpha neutralizing monoclonal antibody, infliximab. Results substantiate the notion of a dual relationship between sleep and AD, whereby A beta Os disrupt sleep/wake patterns and chronic sleep restriction increases brain vulnerability to A beta Os, and point to a key role of brain inflammation in increased susceptibility to A beta Os in sleep-restricted mice. (C) 2017 Elsevier Inc. All rights reserved. (AU) | |
| Processo FAPESP: | 14/50140-6 - Aquisição do sistema de monitoramento integral de animais de laboratório |
| Beneficiário: | Jose Donato Junior |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |