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Folate/vitamin-B12 Prevents Chronic Hyperhomocysteinemia-Induced Tau Hyperphosphorylation and Memory Deficits in Aged Rats.
- Source :
- Journal of Alzheimer's Disease; 2011, Vol. 27 Issue 3, p639-650, 12p
- Publication Year :
- 2011
-
Abstract
- Hyperhomocysteinemia is associated with an increased risk of Alzheimer's disease (AD). Our previous work has demonstrated that combined folate and vitamin B12 (vit-B12) supplementation prevents tau hyperphosphorylation and memory deficits induced by acute administration of homocysteine in young rats. Here, we further investigated whether folate/vit-B12 supplementation is also effective in aged rats with a chronically high level of homocysteine. 18-month-old rats were injected with homocysteine via the vena caudalis with or without a concurrent folate/vit-B12 supplementation for 28 weeks. We found that hyperhomocysteinemia induced tau hyperphosphorylation and accumulation in hippocampus and cortex. Concurrent signaling changes included the activation of glycogen synthase kinases-3β, cyclin-dependent kinase-5, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38MAPK, and inhibition of protein phosphatase 2A. Although the ability to learn was not affected, the aged rats exhibited significant memory deficits. Folate/vit-B12 supplementation attenuated these biochemical and behavioral correlates. These data demonstrate that folate/vit-B12 supplementation is also effective in a chronic hyperhomocysteinemia model in reversing the AD-like tau pathologies and memory deficits. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13872877
- Volume :
- 27
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Alzheimer's Disease
- Publication Type :
- Academic Journal
- Accession number :
- 67478650
- Full Text :
- https://doi.org/10.3233/JAD-2011-110770