Role of caspase-3 in ethanol-induced developmental neurodegeneration.
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.
Young
Chainllie
C
Department of Psychiatry, Campus box 8134, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.
Roth
Kevin A
KA
Klocke
Barbara J
BJ
West
Tim
T
Holtzman
David M
DM
Labruyere
Joann
J
Qin
Yue-Qin
YQ
Dikranian
Krikor
K
Olney
John W
JW
D020268:Alcohol-Induced Disorders, Nervous System / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000633:toxicity; D003593:Cytoplasm / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015388:Organelles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases