PMID:14502238

Citation	Young, C, Klocke, BJ, Tenkova, T, Choi, J, Labruyere, J, Qin, YQ, Holtzman, DM, Roth, KA and Olney, JW (2003) Ethanol-induced neuronal apoptosis in vivo requires BAX in the developing mouse brain. Cell Death Differ. 10:1148-55
Abstract	A single episode of ethanol intoxication triggers widespread apoptotic neurodegeneration in the infant rat or mouse brain. The cell death process occurs over a 6-16 h period following ethanol administration, is accompanied by a robust display of caspase-3 enzyme activation, and meets ultrastructural criteria for apoptosis. Two apoptotic pathways (intrinsic and extrinsic) have been described, either of which may culminate in the activation of caspase-3. The intrinsic pathway is regulated by Bax and Bcl-XL and involves Bax-induced mitochondrial dysfunction and release of cytochrome c as antecedent events leading to caspase-3 activation. Activation of caspase-8 is a key event preceding caspase-3 activation in the extrinsic pathway. In the present study, following ethanol administration to infant mice, we found no change in activated caspase-8, which suggests that the extrinsic pathway is not involved in ethanol-induced apoptosis. We also found that ethanol triggers robust caspase-3 activation and apoptotic neurodegeneration in C57BL/6 wildtype mice, but induces neither phenomenon in homozygous Bax-deficient mice. Therefore, it appears that ethanol-induced neuroapoptosis is an intrinsic pathway-mediated phenomenon involving Bax-induced disruption of mitochondrial membranes and cytochrome c release as early events leading to caspase-3 activation.
Links	PubMed Online version:10.1038/sj.cdd.4401277
Keywords	Animals; Anterior Thalamic Nuclei/drug effects; Anterior Thalamic Nuclei/pathology; Apoptosis/drug effects; Blotting, Western; Brain/drug effects; Brain/pathology; Brain Chemistry/drug effects; Caspase 3; Caspase 8; Caspases/metabolism; Cerebral Cortex/drug effects; Cerebral Cortex/pathology; Cytochromes c/analysis; Ethanol/blood; Ethanol/pharmacology; Genotype; Heterozygote; Hippocampus/drug effects; Hippocampus/pathology; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurodegenerative Diseases/chemically induced; Neurodegenerative Diseases/pathology; Neurons/drug effects; Neurons/pathology; Protein Transport/drug effects; Protein Transport/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-2; Spectrin/analysis; Time Factors; Up-Regulation; bcl-2-Associated X Protein
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