ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: We examined patterns and mechanisms of cell death inducedby haloperidol. Cortical cell cultures exposed to 10-100 μMhaloperidol for 24 h underwent neuronal death without injuring glia. Thedegenerating neurons showed hallmarks of apoptosis, featuring cell bodyshrinkage, nuclear chromatin condensation and aggregation, nuclear membranedisintegration with intact plasma membrane, and prominent internucleosomal DNAfragmentation. Neither glutamate antagonists nor antioxidants prevented thehaloperidol-induced neuronal apoptosis. The c-Jun-NH2-terminalprotein kinase and p38 mitogen-activated protein kinase were activated within1 h and were sustained over the next 3 h following exposure of corticalneurons to 30 μM haloperidol. Haloperidol-induced neuronalapoptosis was partially attenuated by 10-30 μM PD169316, aselective inhibitor of p38 mitogen-activated protein kinase. Inclusion of 1μg/ml cycloheximide, a protein synthesis inhibitor, or 100 ng/ml insulinprevented activation of both kinases and subsequent neuronal death. Thepresent study demonstrates that cortical neurons exposed to haloperidolundergo apoptosis depending on activation of p38 mitogen-activated proteinkinase and c-Jun-NH2-terminal protein kinase sensitive tocycloheximide and insulin.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0752327.x
