Metformin Improves Learning and Memory in the SAMP8 Mouse Model of Alzheimer's Disease.
J Alzheimers Dis
; 68(4): 1699-1710, 2019.
Article
em En
| MEDLINE
| ID: mdl-30958364
ABSTRACT
Metformin is used for the treatment of insulin resistant diabetes. Diabetics are at an increased risk of developing dementia. Recent epidemiological studies suggest that metformin treatment prevents cognitive decline in diabetics. A pilot clinical study found cognitive improvement with metformin in patients with mild cognitive impairment (MCI). Preclinical studies suggest metformin reduces Alzheimer-like pathology in mouse models of Alzheimer's disease (AD). In the current study, we used 11-month-old SAMP8 mice. Mice were given daily injections of metformin at 20âmg/kg/sc or 200âmg/kg/sc for eight weeks. After four weeks, mice were tested in T-maze footshock avoidance, object recognition, and Barnes maze. At the end of the study, brain tissue was collected for analysis of PKC (PKCζ, PKCι, PKCα, PKCγ, PKCÉ), GSK-3ß, pGSK-3ßser9, pGSK-3ßtyr216, pTau404, and APP. Metformin improved both acquisition and retention in SAMP8 mice in T-maze footshock avoidance, retention in novel object recognition, and acquisition in the Barnes maze. Biochemical analysis indicated that metformin increased both atypical and conventional forms of PKC; PKCζ, and PKCα at 20âmg/kg. Metformin significantly increased pGSK-3ßser9 at 200âmg/kg, and decreased Aß at 20âmg/kg and pTau404 and APPc99 at both 20âmg/kg and 200âmg/kg. There were no differences in blood glucose levels between the aged vehicle and metformin treated mice. Metformin improved learning and memory in the SAMP8 mouse model of spontaneous onset AD. Biochemical analysis indicates that metformin improved memory by decreasing APPc99 and pTau. The current study lends support to the therapeutic potential of metformin for AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Neuroprotetores
/
Aprendizagem em Labirinto
/
Doença de Alzheimer
/
Memória
/
Metformina
Limite:
Animals
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2019
Tipo de documento:
Article