Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis.
Biochim Biophys Acta Mol Basis Dis
; 1865(11): 165531, 2019 11 01.
Article
en En
| MEDLINE
| ID: mdl-31398466
ABSTRACT
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are unclear, several risk factors have been identified, including impaired glycemic control, which significantly increases the risk of cognitive decline and AD. In vitro and in vivo studies show that human adenovirus 36 (Ad36) improves glycemic control by increasing cellular glucose uptake in cells, experimental animal models and in humans who are naturally exposed to the virus. This study, tested improvement in glycemic control by Ad36 and delay in onset of cognitive decline in APPswe transgenic mice (Tg2576 line), a model of genetic predisposition to impaired glycemic control and AD. Three-month old APPswe mice were divided into Ad36 infected (Ad36) or mock infected (control) groups and baseline glycemic control measured by glucose tolerance test (GTT) prior to infection. Changes in glycemic control were determined 10- and 24-week post infection. Serum insulin was also measured during GTT. Cognition was determined by Y-maze test, while motor coordination and skill acquisition by rotarod test. Glycemic control as determined by GTT showed less deterioration in Ad36 infected mice over time, accompanied by a significant attenuation of cognitive decline. Analysis of brain tissue lysate showed significantly reduced levels of amyloid beta 42 in Ad36 mice relative to control mice. Golgi-Cox staining analysis also revealed reduced dendritic spines and synaptic gene expression in control mice compared to Ad36 infected mice. This proof of concept study shows that in a mouse model of AD, Ad36 improves glycemic control and ameliorates cognitive decline.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adenoviridae
/
Infecciones por Adenoviridae
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Enfermedad de Alzheimer
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Disfunción Cognitiva
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2019
Tipo del documento:
Article