Effects of alpha-tocopherol on an animal model of tauopathies.
We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them alpha-tocopherol, the major component of antioxidant vitamin E. Supplementation of alpha-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like alpha-tocopherol may prevent neurodegenerative tauopathies.
Nakashima
Hanae
H
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho, 700-8558, Japan.
Ishihara
Takeshi
T
Yokota
Osamu
O
Terada
Seishi
S
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
Kuroda
Shigetoshi
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D002490:Central Nervous System / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019636:Neurodegenerative Diseases / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D013116:Spinal Cord / Q000473:pathology; D024801:Tauopathies / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors; D019076:Transgenes; D024502:alpha-Tocopherol / Q000494:pharmacology*; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics
D000975:Antioxidants; D020033:Protein Isoforms; D016875:tau Proteins; D024502:alpha-Tocopherol; D010100:Oxygen