Rapid alteration of tau in oligodendrocytes after focal ischemic injury in the rat: involvement of free radicals.
Glial inclusions containing the microtubule-associated protein tau are present in a variety of chronic neurodegenerative conditions. We now report a rapid and time-dependent increase of tau immunoreactivity within oligodendrocytes after focal cerebral ischemia in the rat. The number of tau positive oligodendrocytes in the ipsilateral subcortical white matter increased six- to eightfold by 40 minutes after permanent middle cerebral artery occlusion (MCAO). Tau was detected using antibodies that label both the N- and C-terminal of the protein, suggesting accumulation of full-length protein within these cells. Pretreatment with the spin trap agent alpha-phenyl-tert-butyl-nitrone (PBN)(100mg/kg) reduced the number of tau-positive oligodendrocytes by 55% in the subcortical white matter of the ischemic hemisphere compared with untreated animals at 40 minutes after MCAO. In contrast, pretreatment with glutamate receptor antagonists MK-801 (0.5 mg/kg) or 2,3-dihydroxy-6-nitro-7-sulpfamoyl-benzo(f)quinoxaline (NBQX) (2 x 30 mg/kg), failed to reduce the number of tau-positive oligodendrocytes after 40 minutes of ischemia. The results indicate that oligodendrocytes respond rapidly to an ischemic challenge and that free radical-mediated mechanisms are involved in the cascade leading to increased tau immunoreactivity.
Irving
E A
EA
Wellcome Surgical Institute, University of Glasgow, Scotland, United Kingdom.
Yatsushiro
K
K
McCulloch
J
J
Dewar
D
D
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002421:Caudate Nucleus / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005609:Free Radicals; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009589:Nitrogen Oxides / Q000494:pharmacology; D009836:Oligodendroglia / Q000737:chemistry* / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013113:Spin Labels; D016875:tau Proteins / Q000032:analysis* / Q000187:drug effects
D003497:Cyclic N-Oxides; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D008869:Microtubule-Associated Proteins; D009589:Nitrogen Oxides; D011810:Quinoxalines; D013113:Spin Labels; D016875:tau Proteins; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C029217:phenyl-N-tert-butylnitrone; D016291:Dizocilpine Maleate