title: Folate/vitamin-B12 prevents chronic hyperhomocysteinemia-induced tau hyperphosphorylation and memory deficits in aged rats.
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.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Neurological Disease of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Liu
authors.forename: Chang-E
authors.initials: CE
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Zelan
authors.initials: Z
authors.lastname: Wei
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Mousseau
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Gong-Ping
authors.initials: GP
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D002908:Chronic Disease; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005492:Folic Acid / Q000008:administration & dosage*; D020138:Hyperhomocysteinemia / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D008569:Memory Disorders / Q000378:metabolism* / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014805:Vitamin B 12 / Q000008:administration & dosage*; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D005492:Folic Acid; D014805:Vitamin B 12