Prolonged isolation stress accelerates the onset of Alzheimer's disease-related pathology in 5xFAD mice despite running wheels and environmental enrichment.
Behav Brain Res
; 379: 112366, 2020 02 03.
Article
em En
| MEDLINE
| ID: mdl-31743728
ABSTRACT
Research has demonstrated that stress can exacerbate AD pathology in transgenic mouse models of AD. The purpose of the present studies was to extend this work by determining whether a social stressor, isolation stress, would increase the number of Aß plaques in 5xFAD + transgenic mice in comparison to group-housed controls, and accelerate the onset of cognitive deficits in contextual fear-conditioning. Additionally, we aimed to determine whether the pathological impact of isolation stress could be prevented through exposure to exercise alone or to exercise and an enriched environment throughout the isolation period. Two-month-old 5xFAD + and 5xFAD- animals were isolated or group-housed for two and three months. An additional subset of 5xFAD + mice were housed in isolation, housed in isolation with an exercise wheel, or housed in isolation with an exercise wheel and an enriched environment. Both two and three months of isolation stress significantly increased the number of plaques in the hippocampus of 5xFAD + mice, and three months of isolation increased hippocampal BACE1 expression. Isolated animals also displayed a significant cognitive deficit in contextual fear-conditioning, independent of genotype. Furthermore, neither exercise nor an enriched environment were able to prevent these isolation-induced effects. Understanding how stress impacts the onset and progression of AD is critical, as many individuals endure significant stress over their lifespan, including prolonged social isolation, a societal trend likely to worsen with time.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Condicionamento Físico Animal
/
Isolamento Social
/
Estresse Psicológico
/
Ácido Aspártico Endopeptidases
/
Placa Amiloide
/
Secretases da Proteína Precursora do Amiloide
/
Doença de Alzheimer
/
Disfunção Cognitiva
/
Hipocampo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos