Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.
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.
Ikonomidou
C
C
Department of Pediatric Neurology, Charité-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. hrissanthi.ikonomidou@charite.de
Bosch
F
F
Miksa
M
M
Bittigau
P
P
Vöckler
J
J
Dikranian
K
K
Tenkova
T I
TI
Stefovska
V
V
Turski
L
L
Olney
J W
JW
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D006220:Haloperidol / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009410:Nerve Degeneration; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D012601:Scopolamine; D006220:Haloperidol