Ethanol-induced neuronal apoptosis in vivo requires BAX in the developing mouse brain

C. Young, B. J. Klocke, T. Tenkova, J. Choi, J. Labruyere, Y. Q. Qin, D. M. Holtzman, K. A. Roth, J. W. Olney

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192 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1148-1155
Number of pages8
JournalCell Death and Differentiation
Issue number10
Publication statusPublished - 2003 Oct 1

Bibliographical note

Funding Information:
This research was supported by NIH grants AG 11355, DA 05072, HD 37100, NS 35107. JWO is a NARSAD 2000 Toulmin Distinguished Investigator Awardee.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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