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
