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Science 11 February 2000:
Vol. 287. no. 5455, pp. 1056 - 1060
DOI: 10.1126/science.287.5455.1056
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Reports

Ethanol-Induced Apoptotic Neurodegeneration and Fetal Alcohol Syndrome

Chrysanthy Ikonomidou, 1 Petra Bittigau, 1 Masahiko J. Ishimaru, 2 David F. Wozniak, 3 Christian Koch, 1 Kerstin Genz, 1 Madelon T. Price, 3 Vanya Stefovska, 1 Friederike Hörster, 1 Tanya Tenkova, 3 Krikor Dikranian, 3 John W. Olney 3*

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 GABAA 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.

1 Department of Pediatric Neurology, Charité, Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
2 Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyodku, Tokyo, Japan.
3 Department of Psychiatry, Washington University School of Medicine, 4940 Children's Place, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed.

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