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- Title
Folate/vitamin-B12 Prevents Chronic Hyperhomocysteinemia-Induced Tau Hyperphosphorylation and Memory Deficits in Aged Rats.
- Authors
Wei, Wei; Liu, Ying-Hua; Zhang, Chang-E.; Wang, Qun; Wei, Zelan; Mousseau, Darrell D.; Wang, Jian-Zhi; Tian, Qing; Liu, Gong-Ping
- 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.
- Subjects
MEDICAL research; HYPERHOMOCYSTEINEMIA; PHOSPHORYLATION; MEMORY disorders; LABORATORY rats; FOLIC acid; VITAMIN B12
- Publication
Journal of Alzheimer's Disease, 2011, Vol 27, Issue 3, p639
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2011-110770