Abstract
Acute, transient exposure to ethanol causes a widespread pattern of caspase-3 activation and neuroapoptosis in the developing rodent brain. To determine whether caspase-3 activation is an essential step in ethanol-induced developmental neuroapoptosis, we treated homozygous caspase-3 knockout mice or wild-type mice on postnatal day 7 with an apoptosis-inducing dose of ethanol and examined the brains at appropriate survival times for evidence of apoptotic neurodegeneration. In caspase-3 knockout mice, the cell death process evolved more slowly than in wild-type mice, and morphological changes observed were not those typically associated with apoptosis. However, neuronal cell counts performed 2 weeks post-treatment revealed that the extent of neuron loss was similar in wild-type and caspase-3-deficient mice. We conclude that absence of functional caspase-3 alters the time course and morphological characteristics of the neurodegenerative process but does not prevent ethanol-induced neuron death.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alcohol-Induced Disorders, Nervous System / enzymology*
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Alcohol-Induced Disorders, Nervous System / genetics
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Alcohol-Induced Disorders, Nervous System / pathology
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Animals
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Animals, Newborn
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Apoptosis / drug effects*
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Apoptosis / physiology
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Brain / drug effects*
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Brain / enzymology*
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Brain / pathology
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Caspase 3
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Caspases / genetics*
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Central Nervous System Depressants / toxicity
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Cytoplasm / drug effects
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Cytoplasm / pathology
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Cytoplasm / ultrastructure
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Disease Models, Animal
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Ethanol / toxicity*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microscopy, Electron, Transmission
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Nerve Degeneration / chemically induced*
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Nerve Degeneration / genetics
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Nerve Degeneration / pathology
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Neurons / drug effects
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Neurons / enzymology
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Neurons / pathology
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Organelles / drug effects
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Organelles / pathology
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Organelles / ultrastructure
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Time Factors
Substances
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Central Nervous System Depressants
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Ethanol
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Casp3 protein, mouse
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Caspase 3
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Caspases