Exposure to pyrithiamine increases ß-amyloid accumulation, Tau hyperphosphorylation, and glycogen synthase kinase-3 activity in the brain.
Neurotox Res
; 19(4): 575-83, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-20567953
ABSTRACT
Decreased thiamine-dependent enzyme activity and/or thiamine deficiency (TD) have been linked to Alzheimer's disease (AD). In this study, we administered pyrithiamine, an anti-thiamine compound, to both APP/PS1 transgenic mice and wild-type littermate control mice; alternatively, we induced TD by thiamine-depleted diet. Pyrithiamine treatment and diet-induced TD impaired the memory of wild-type mice, but had little effect on APP/PS1 mice. Pathophysiologically, pyrithiamine treatment and diet-induced TD aggravated ß-amyloid accumulation in the brain. This was demonstrated by increased ß-amyloid in the brains of wild-type mice using ELISA and by the number of amyloid plaques in the brains of APP/PS1 transgenic mice using immunochemical staining. Also, enhanced numbers of phosphorylated Tau-positive cells were observed in both APP/PS1 transgenic and wild-type mice. Furthermore, pyrithiamine decreased the phosphorylation rates of glycogen synthase kinase (GSK)-3ß and raised its enzymatic activity, but had little influence on GSK-3α. Diet-induced TD reduced the phosphorylated rates and increased the activities of GSK-3, GSK-3α, and GSK-3ß. These results suggest that when sufficient thiamine supplement is administered, pyrithiamine can cause AD-like pathological alterations similar to that of diet-induced TD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piritiamina
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Encéfalo
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Péptidos beta-Amiloides
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Proteínas tau
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Glucógeno Sintasa Quinasa 3
Límite:
Animals
Idioma:
En
Revista:
Neurotox Res
Asunto de la revista:
NEUROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
China