title: Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer's disease - Hyperphosphorylation and cleavage of 4- and 3-repeat tau.
abstract: Epidemiological studies have suggested a close relationship between cerebral ischemia and Alzheimer's disease (AD). To clarify the pathological association of tau dynamics in both diseases, we performed comprehensive studies on the posttranslational modification of tau in cerebral ischemia and reperfusion (I/R) in rats. The present study suggests that both 4-repeat and 3-repeat tau isoforms are hyperphosphorylated in cerebral I/R, similar to the case in AD. The generation of a 60-kDa Asp421-truncated tau in cerebral I/R preceded the emergence of a 17-kDa 3-repeat tau fragment and a 25-kDa 4-repeat tau fragment. The regional redistribution of tau from the neuropil to neuronal perikarya in our stroke model is thought to share similarity with that occurring in AD. In addition, immunofluorescence staining revealed the formation of axonal varicosities in cerebral I/R. Altered tau distribution may influence microtubule stability, disturbances in axonal transport, and the resulting formation of axonal varicosities. The staining profiles of granules in the ischemic cortex that were immunopositive for RD3, RD4, and AT8 in neuronal perikarya and that were argyrophilic on Gallyas-Braak staining were similar to those in AD. These findings suggest that transient cerebral ischemia shares a common pathology with AD, in the modification of tau protein.
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.|2 Department of Stroke Medicine, Kawasaki Medical School Hospital, Kawasaki, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mukai
authors.affiliation: 3 Department of Molecular and Pharmacological Neuroscience, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: 3 Department of Molecular and Pharmacological Neuroscience, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.affiliation: 1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins
keywords: Alzheimer’s disease; cerebral ischemia; cleavage; phosphorylation; tau