mTOR-mediated hyperphosphorylation of tau in the hippocampus is involved in cognitive deficits in streptozotocin-induced diabetic mice.
Metab Brain Dis
; 29(3): 729-36, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24682776
ABSTRACT
Abnormal levels of mammalian target of rapamycin (mTOR) signaling have been recently implicated in the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease (AD). However, the implication of mTOR in diabetes mellitus (DM)-related cognitive dysfunction still remains unknown. In the present study, we found that phosphorylated mTOR at Ser2448, phosphorylated p70S6K at Thr421/Ser424 and phosphorylated tau at Ser396 were significantly increased in the hippocampus of streptozotocin (STZ)-induced diabetic mice when compared with control mice. A low dose of rapamycin was used to elucidate the role of mTOR signaling in DM-related cognitive deficit. Rapamycin restored abnormal mTOR/p70S6K signaling and attenuated the phosphorylation of tau protein in the hippocampus of diabetic mice. Furthermore, the spatial learning and memory function of diabetic mice significantly impaired compared with control mice, was also reversed by rapamycin. These findings indicate that mTOR/p70S6K signaling pathway is hyperactive in the hippocampus of STZ-induced diabetic mice and inhibiting mTOR signaling with rapamycin prevents the DM-related cognitive deficits partly through attenuating the hyperphosphorylation of tau protein.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
/
Transtornos Cognitivos
/
Diabetes Mellitus Experimental
/
Serina-Treonina Quinases TOR
/
Hipocampo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Metab Brain Dis
Assunto da revista:
CEREBRO
/
METABOLISMO
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China