Sequence of neurodegeneration and accumulation of phosphorylated tau in cultured neurons after okadaic acid treatment

被引:70
作者
Kim, D
Su, J
Cotman, CW
机构
[1] Univ Ulsan, Coll Med, Dept Anat, Seoul 138736, South Korea
[2] Univ Calif Irvine, Inst Brain Aging & Dementia, Dept Psychobiol, Irvine, CA 92697 USA
关键词
okadaic acid; tau phosphorylation; neurofibrillary tangle; dystrophic neurite;
D O I
10.1016/S0006-8993(99)01724-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Within neurofibrillary tangles and dystrophic neurites of Alzheimer's disease (AD), the cytoskeletal protein tau is abnormally hyperphosphorylated. In the present study, we examined the effect of okadaic acid (OA), a protein phosphatase inhibitor, in rat cultured neurons. Low concentrations of OA induce degeneration of neurites, rounding of cell bodies, detachment from the substratum, and eventual neuronal death. During OA-induced degeneration, SMI-31 immunoreactivity became punctate in neurites at 6 h after OA treatment, and over time, accumulated in cell bodies and dystrophic neurites. Hyperphosphorylation of tau and marked loss of MAP-2-positive dendrites occurred after 6 h of treatment with OA. Thereafter, AT-8 and PHF-1 immunoreactivity accumulated in cell bodies and subsequently appeared in distal axon-like neurites. These results demonstrate that OA treatment induced hyperphosphorylation of tau and preferential dendritic damage, with subsequent accumulation of phosphorylated tau in cell bodies and dystrophic axon-like neurites. OA-induced neurodegeneration may provide a useful model to study AD. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:253 / 262
页数:10
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