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Science 1 January 1999:
Vol. 283. no. 5398, pp. 70 - 74
DOI: 10.1126/science.283.5398.70
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Reports

Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain

Chrysanthy Ikonomidou, * Friederike Bosch, Michael Miksa, Petra Bittigau, Jessica Vöckler, Krikor Dikranian, Tanya I. Tenkova, Vanya Stefovska, Lechoslaw Turski, John W. Olney

Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.

C. Ikonomidou, F. Bosch, M. Miksa, P. Bittigau, J. Vöckler, V. Stefovska, Department of Pediatric Neurology, Charité-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. K. Dikranian, T. I. Tenkova, J. W. Olney, Department of Psychiatry, Washington University School of Medicine, 4940 Children's Place, St. Louis, MO 63110, USA. L. Turski, Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, London WC1E 6BT, UK.
*   To whom correspondence should be addressed: E-mail: hrissanthi.ikonomidou{at}charite.de

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In Utero Ethanol Suppresses Cerebellar Activator Protein-1 and Nuclear Factor-kappa B Transcriptional Activation in a Rat Fetal Alcohol Syndrome Model.
G. K. Acquaah-Mensah, J. P. Kehrer, and S. W. Leslie (2002)
J. Pharmacol. Exp. Ther. 301, 277-283
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Excitotoxicity: Perspectives Based on N-Methyl-D-Aspartate Receptor Subtypes.
D. R. Lynch and R. P. Guttmann (2002)
J. Pharmacol. Exp. Ther. 300, 717-723
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Activation of Neuronal N-Methyl-D-Aspartate Receptor Channels by Lipid Emulsions.