title: High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice.
abstract: Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kook
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: K-M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Cha
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Baik
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: R
authors.initials: R
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: I
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D050544:L-Gulonolactone Oxidase / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid