Insulin deficiency, but not resistance, exaggerates cognitive deficits in transgenic mice expressing human amyloid and tau proteins. Reversal by Exendin-4 treatment.
J Neurosci Res
; 98(11): 2357-2369, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32737929
ABSTRACT
Epidemiological studies have pointed at diabetes as a risk factor for Alzheimer's disease (AD) and this has been supported by several studies in animal models of both type 1 and type 2 diabetes. However, side-by-side comparison of the two types of diabetes is limited. We investigated the role of insulin deficiency and insulin resistance in the development of memory impairments and the effect of Exendin-4 (Ex4) treatment in a mouse model of AD. Three-4-month-old female wild type (WT) mice and mice overexpressing human tau and amyloid precursor protein (TAPP) were injected with streptozotocin (STZ) or fed a high-fat diet (HFD). A second study was performed in TAPP-STZ mice treated with Ex4, a long-lasting analog of GLP-1. Plasma and brain were collected at study termination for ELISA, Western blot, and immunohistochemistry analysis. Learning and memory deficits were impaired in TAPP transgenic mice compared with WT mice at the end of the study. Deficits were exaggerated by insulin deficiency in TAPP mice but 12 weeks of insulin resistance did not affect memory performances in either WT or TAPP mice. Levels of phosphorylated tau were increased in the brain of WT-STZ and TAPP-STZ mice but not in the brain of WT or TAPP mice on HFD. In the TAPP-STZ mice, treatment with Ex4 initiated after established cognitive deficits ameliorated learning, but not memory, impairments. This was accompanied by the reduction of amyloid ß and phosphorylated tau expression. Theses studies support the role of Ex4 in AD, independently from its actions on diabetes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Precursor de Proteína beta-Amiloide
/
Proteínas tau
/
Transtornos Cognitivos
/
Exenatida
/
Hipoglicemiantes
/
Insulina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article