Alcohol-induced neuroapoptosis in the fetal macaque brain.
The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fascicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8h, then the fetuses were delivered by caesarean section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD.
Farber
Nuri B
NB
Department of Psychiatry, Washington University, St. Louis, MO 63110-1093, USA. farbern@psychiatry.wustl.edu
Creeley
Catherine E
CE
Olney
John W
JW
D020268:Alcohol-Induced Disorders, Nervous System / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000633:toxicity; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D008252:Macaca fascicularis; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013995:Time
D002492:Central Nervous System Depressants; D000431:Ethanol