Ethanol-induced apoptosis in the developing visual system during synaptogenesis.
OBJECTIVE
Ethanol is known to have deleterious effects on the human fetal nervous system (fetal alcohol syndrome), including components of the visual system, but only modest progress has been made in understanding these effects. The authors have recently demonstrated that, during the period of synaptogenesis, a single episode of ethanol intoxication lasting for several hours triggers a massive wave of apoptotic neurodegeneration in several regions of the developing rat or mouse forebrain. The present study was undertaken to determine to what extent the developing visual system is vulnerable to the apoptogenic effects of ethanol.


METHODS
Infant rats and mice at ages from birth to 21 days were treated subcutaneously with a single dose of ethanol or with two doses, 2 hours apart, on a single day. Blood alcohol levels were determined, and the retinas and visual centers in the brain were examined by light and electronmicroscopy at various times from 4 to 24 hours after treatment.


RESULTS
Retinal ganglion cells and neurons in the lateral geniculate nucleus, superior colliculus, and visual cortex were all highly susceptible to ethanol's apoptogenic action, the period of peak sensitivity being postnatal days 1 to 4 for ganglion cells and 4 to 7 for the other visual neurons. A transient elevation of blood alcohol to approximately 120 mg/dL was sufficient to activate the cell death program in visual neurons.


CONCLUSIONS
During synaptogenesis, a single ethanol intoxication episode triggers apoptotic cell death of neurons at all levels of the visual system from retina to the visual cortex.
Tenkova
Tatyana
T
Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Young
Chainllie
C
Dikranian
Krikor
K
Labruyere
Joann
J
Olney
John W
JW
D020268:Alcohol-Induced Disorders, Nervous System / Q000209:etiology* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005829:Geniculate Bodies / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D013477:Superior Colliculi / Q000187:drug effects / Q000473:pathology; D013569:Synapses / Q000187:drug effects*; D014793:Visual Cortex / Q000187:drug effects / Q000473:pathology; D014795:Visual Pathways / Q000187:drug effects* / Q000473:pathology
D000431:Ethanol