Cooperative effects of amyloid beta (25--35) and hypoxia-reoxygenation on cell death in primary cultured neurons of mouse cerebral cortex.

摘要

Amyloid beta protein participates in the neurodegenerative process of Alzheimer's disease (AD). A substantial body of evidence indicates that oxidative stress is involved in amyloid beta-induced neurotoxicity. Hypoxia-reoxygenation (HR), a common clinical condition that overlaps the age range of AD clinical presentation, can result in neuronal cell injury. Neuronal cell loss in HR is mediated, at least in part, via the generation of reactive oxygen species (ROS). We here examined neuronal cell loss following amyloid beta peptide (Abeta), HR, or both in primary cultured mouse cortical neurons. Abeta pre-treated neurons were exposed to 12hrs of 0.1% hypoxia followed by 12 or 24hrs of 21% oxygen. Taken together, the findings suggest that AP and HR may act cooperatively to induce neuronal cell death through both apoptosis and necrosis, and that mitochondrial dysfunction and excessive ROS generation appear to be involved in such processes. (Abstract shortened by UMI.)