Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.
The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.
Ikonomidou
C
C
Department of Pediatric Neurology, Charité, Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
Bittigau
P
P
Ishimaru
M J
MJ
Wozniak
D F
DF
Koch
C
C
Genz
K
K
Price
M T
MT
Stefovska
V
V
Hörster
F
F
Tenkova
T
T
Dikranian
K
K
Olney
J W
JW
D000818:Animals; D017209:Apoptosis; D001569:Benzodiazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D009410:Nerve Degeneration; D009474:Neurons / Q000166:cytology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D018757:GABA Modulators; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D000431:Ethanol