Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B.
Exp Gerontol
; 104: 66-71, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29421605
ABSTRACT
The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, ß-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats. Young (3â¯months) and middle-aged (17â¯months) Wistar rats were submitted to Morris-water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3ß, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and ß-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Tirosina Fosfatase não Receptora Tipo 1
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Aprendizagem Espacial
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Hipocampo
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Insulina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Gerontol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil