Isoflurane-induced apoptosis: A potential pathogenic link between delirium and dementia

被引:96
作者
Xie, Zhongcong
Dong, Yuanlin
Maeda, Uta
Moir, Robert
Inouye, Sharon K.
Culley, Deborah J.
Crosby, Gregory
Tanzi, Rudolph E.
机构
[1] Harvard Univ, Sch Med,MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA
[2] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02115 USA
[4] Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, Boston, MA USA
[5] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Boston, MA 02115 USA
来源
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2006年 / 61卷 / 12期
关键词
D O I
10.1093/gerona/61.12.1300
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Background. Dementia and delirium have been postulated to share common pathophysiologic mechanisms; however, identification of these unifying mechanisms has remained elusive. The inhalation anesthetic isoflurane has been shown to enhance P-amyloid protein (A beta) oligomerization and generation, to potentiate the cytotoxicity of A beta, and to induce apoptosis. To address the molecular mechanisms of dementia and delirium associated with anesthesia and surgery, we assessed whether the A fibrillar aggregation inhibitor Congo red can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells overexpressing human beta-amyloid precursor protein (APP). Methods. H4 human neuroglioma cells stably transfected to express human full-length wild-type APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the end of the treatment. Caspase-3 activation was measured with quantitative Western blotting. Results. We found that isoflurane induces cellular apoptosis in a dose-dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4 human neuroglioma cells overexpressing APP. Interestingly, Congo red also inhibits staurosporine-induced apoptosis. Conclusion. The demonstration that isoflurane contributes to well-described mechanisms of Alzheimer's neuropathogenesis provides a plausible link between the acute effects of anesthesia, a well-described risk factor for delirium, and the more long-term sequelae of dementia. These findings suggest that isoflurane-induced A beta oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia.
引用
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页码:1300 / 1306
页数:7
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