Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain.
Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period (first 2 weeks after birth), triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain. While synaptogenesis is largely a postnatal phenomenon in rats, it occurs prenatally (last trimester of pregnancy) in humans. Recent evidence strongly supports the interpretation that ethanol exerts its apoptogenic action by a dual mechanism--blockade of NMDA glutamate receptors and hyperactivation of GABA(A) receptors. These findings in immature rats represent a significant advance in the fetal alcohol research field, in that previous in vivo animal studies had not demonstrated an apoptogenic action of ethanol, had not documented ethanol-induced cell loss from more than a very few brain regions and had not provided penetrating insight into the mechanisms underlying ethanol's neurotoxic action. To add to the mechanistic insights recently gained, it would be desirable to examine gene-regulated aspects of ethanol-induced apoptotic neurodegeneration, using genetically altered strains of mice. The feasibility of such research must first be established by demonstrating that appropriate mouse strains are sensitive to this neurotoxic mechanism. In the present study, we demonstrate that mice of the C57BL/6 strain, a strain frequently used in transgenic and gene deletion research, are exquisitely sensitive to the mechanism by which ethanol induces apoptotic neurodegeneration during the synaptogenesis period of development.
Olney
John W
JW
Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. olneyj@psychiatry.wustl.edu
Tenkova
Tatyana
T
Dikranian
Krikor
K
Qin
Yue-Qin
YQ
Labruyere
Joann
J
Ikonomidou
Chrysanthy
C
D020268:Alcohol-Induced Disorders, Nervous System / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013997:Time Factors
D000431:Ethanol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases