Chronic intermittent hypoxia/reoxygenation facilitate amyloid-ß generation in mice.
J Alzheimers Dis
; 37(2): 325-33, 2013.
Article
em En
| MEDLINE
| ID: mdl-23948880
ABSTRACT
Previous studies have shown a high prevalence of obstructive sleep apnea (OSA) among patients with Alzheimer's disease (AD). However, it is poorly assessed whether chronic intermittent hypoxia (CIH), which is a characteristic of OSA, affects the pathophysiology of AD. We aimed to investigate the direct effect of intermittent hypoxia (IH) in pathophysiology of AD in vivo and in vitro. In vivo, 15 male triple transgenic AD mice were exposed to either CIH or normoxia (5% O2 and 21% O2 every 10 min, 8 h/day for 4 weeks). Amyloid-ß (Aß) profile, cognitive brain function, and brain pathology were evaluated. In vitro, human neuroblastoma SH-SY5Y cells stably expressing wild-type amyloid-ß protein precursor were exposed to either IH (8 cycles of 1% O2 for 10 min followed by 21% O2 for 20 min) or normoxia. The Aß profile in the conditioned medium was analyzed. CIH significantly increased levels of Aß42 but not Aß40 in the brains of mice without the increase in hypoxia-inducible factor 1, alpha subunit (HIF-1α) expression. Furthermore, CIH significantly increased intracellular Aß in the brain cortex. There were no significant changes in cognitive function. IH significantly increased levels of Aß42 in the medium of SH-SY5Y cells without the increase in the HIF-1α expression. CIH directly and selectively increased levels of Aß42 in the AD model. Our results suggest that OSA would aggravate AD. Early detection and intervention of OSA in AD may help to alleviate the progression of the disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Doença de Alzheimer
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Oxigenoterapia Hiperbárica
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Hipóxia
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2013
Tipo de documento:
Article