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Background and Purpose-An animal model of chronic cerebral hypoperfusion was developed with coiled clips applied to both carotid arteries of adult Mongolian gerbils for between 1 week and 2 months. In the brain of this animal model, rarefaction of white matter with dilatation of the ventricles was frequently observed. To better understand the mechanism of white matter alteration under cerebral hypoperfusion, the chronological sequence of molecular changes in the cerebral white matter of the animal model was determined. Methods-Specially designed coiled clips were placed around both carotid arteries of Mongolian gerbils to create stenosis without occlusion. Changes in levels of myelin basic protein (MBP) as a marker of myelin, neurofilament H (NFH) as a marker of axonal proteins, and glial fibrillary acidic protein (GFAP) in astroglia after 2 months of cerebral hypoperfusion were analyzed with Western blotting and enzyme-linked immunosorbent assay. Results-Western blotting of the white matter after 2 months of hypoperfusion showed that the levels of MBP and NFH decreased, whereas that of GFAP increased. The time course of MBP and NFH changes determined with enzyme-linked immunosorbent assay revealed that the change of MBP preceded that of NFH. Conclusions-In the present study it was shown that the damage to myelin precedes that to the axon in the white matter in a chronic cerebral hypoperfusion animal model, suggesting that the change in myelin is the primary pathological event in the cerebral white matter under chronic hypoperfusion. The present study may help in understanding the mechanisms of white matter pathology in leukoaraiosis.

The microtubule-associated protein tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) brain. To date, 21 phosphorylated sites of tau have been identified. In the present study the levels of phosphorylation at Ser199/Ser202, Thr231/Ser235, Ser262/Ser356 and Ser396/Ser404 of tau in AD brain homogenate and its 100,000 x g supernatant were determined using radioimmuno-dot-blot assay. In homogenate, Ser199/Ser202 and Ser262/Ser356 were phosphorylated to similar level and were more phosphorylated than Thr231 or Ser396/Ser404. In supernatant, there was no significant difference in phosphorylated tau level among the investigated sites except for Thr231/Ser235 which was least phosphorylated. These results suggest that Ser199/Ser202 and Ser262/Ser356 are major sites of phosphorylation of tau in AD brain.

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Key words postmortem cerebrospinal fluid

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