Ethanol-induced caspase-3 activation in the in vivo developing mouse brain.
Recently several methods have been described for triggering extensive apoptotic neurodegeneration in the developing in vivo mammalian brain. These methods include treatment with drugs that block NMDA glutamate receptors, drugs that promote GABA(A) neurotransmission, or treatment with ethanol, which has both NMDA antagonist and GABAmimetic properties. A single intoxication episode induced by any of these agents is sufficient to cause widespread neurodegeneration throughout many brain regions. The cell death process transpires rapidly from early to late stages within several hours. As the neurons die, they become TUNEL positive and show, by both light and electron microscopy, all of the classical morphological characteristics of apoptosis. In the present study, using immunocytochemical methods, we document that ethanol intoxication of 7-day-old infant mice causes a widespread pattern of caspase-3 activation corresponding to the pattern of apoptotic neurodegeneration that is occurring simultaneously.
Olney
John W
JW
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Tenkova
Tatyana
T
Dikranian
Krikor
K
Muglia
Louis J
LJ
Jermakowicz
Walter J
WJ
D'Sa
Cleta
C
Roth
Kevin A
KA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D012680:Sensitivity and Specificity; D016622:Silver Staining; D012965:Sodium Chloride / Q000494:pharmacology
D002492:Central Nervous System Depressants; D000431:Ethanol; D012965:Sodium Chloride; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases