PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie

被引:172
作者
Williams, A
Lucassen, PJ
Ritchie, D
Bruce, M
机构
[1] MRC,NEUROPATHOGENESIS UNIT,EDINBURGH EH9 3JF,MIDLOTHIAN,SCOTLAND
[2] NETHERLANDS INST BRAIN RES,GRAD SCH NEUROSCI,NL-1105 AZ AMSTERDAM,NETHERLANDS
[3] LEIDEN AMSTERDAM CTR DRUG RES,DIV MED PHARMACOL,NL-2300 RA LEIDEN,NETHERLANDS
关键词
PRION PROTEIN; CELL-DEATH; FRAGMENTED DNA; INFECTED MICE; BRAIN; LOCALIZATION; MICROSCOPY; INSITU; RAT;
D O I
10.1006/exnr.1997.6424
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study investigated the relationship among PrP deposition, microglial activation, vacuolation, and neuronal death in the hippocampus of the 301V/VM murine scrapie model (mean incubation period 117 +/- 1 days). PrP deposition was first detected after 30 days and microglial activation after 60 days. Vacuolation in the CA1 and CA2 pyramidal layer was present from 90 days onward. Only occasional in situ end labeling (ISEL)-positive neurons were present in the hippocampus of scrapie-infected mice from 75 days postinoculation (d.p.i.), except at 105 d.p.i, when relatively large numbers of apoptotic, ISEL-positive neurons in the CA1 hippocampal region were observed. Terminally ill animals showed almost complete loss of CA1 pyramidal neurons. Electron microscopy of the CA1 region at 105 days confirmed that these neurons were dying by apoptosis. These data suggest that microglial activation in scrapie is a response to abnormal PrP deposition rather than a response to neuronal cell loss. (C) 1997 Academic Press.
引用
收藏
页码:433 / 438
页数:6
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