NEUROTOXICITY OF BETA-AMYLOID PROTEIN - CYTOCHEMICAL CHANGES AND APOPTOTIC CELL-DEATH INVESTIGATED IN ORGANOTYPIC CULTURES

被引:18
作者
ALLEN, YS
DEVANATHAN, PH
OWEN, GP
机构
[1] Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool
关键词
APOPTOSIS; BETA-AMYLOID; ORGANOTYPIC CULTURES; NEUROTOXICITY;
D O I
10.1111/j.1440-1681.1995.tb02021.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. This study is an attempt to examine in vitro the cytochemical changes in hippocampal neurones induced by beta-amyloid protein (beta-AP). 2. The mechanism of cell death, and the vulnerability of different regions of the hippocampus to b-AP toxicity, has also been explored using TUNEL staining to locate fragmented DNA in both dissociated and organotypic cultures. 3. Apoptotic cell profiles and the detection by immunocytochemistry of ubiquitin and tau protein confirmed the acute neurodegenerative effects of b-AP, and organotypic cultures revealed the dentate gyrus to be especially vulnerable. 4. A scrambled sequence of b-AP, a peptide with similar hydrophobic groups to b-AP, and islet pancreatic amyloidogenic peptide also showed neurodegenerative effects, although less severely than b-AP. 5. It is concluded that organotypic cultures provide a valuable in vitro model with which to observe and characterize the neurotoxic effects of b-AP. These effects, however, may be non-specific and related more to the general amyloidogenicity of the b-AP molecule.
引用
收藏
页码:370 / 371
页数:2
相关论文
共 5 条
[1]  
Caeser M., Smith D.W., Kemp J.A., Sirinathsinghji D., Beta (25–35)‐amyloid peptide does not produce toxicity in organtypic cultures of the rat hippocampus, European Journal of Neuroscience, (1993)
[2]  
Forloni G., Chiesn R., Smiroldo S., Et al., Apoptosis mediated neurotoxicity induced by chronic application of beta‐amyloid fragment 25–35, Neuroreport, 4, pp. 523-526, (1993)
[3]  
Gavrieli Y., Sherman Y., Ben-Sasson S.A., Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation, Journal of Cell Biology, 119, pp. 493-501, (1992)
[4]  
Malouf A.T., Effect of beta amyloid peptides on neurons in hippocampal slice cultures, Neurobiology of Aging, 13, pp. 543-551, (1992)
[5]  
Yankner B.A., Duffy L.K., Kirschner D.A., Neurotrophic and neurotoxic effects of amyloid beta protein: Reversal by tachykinin neuropeptides, Science, 250, pp. 279-282, (1990)