Excitatory amino acid neurotoxicity in the developing brain.
EAA neurotransmitters participate in a variety of physiologic processes during central nervous system development. EAAs function as neurotransmitters but also regulate development of neuronal cytoarchitecture and neuronal connectivity. EAAs play a major role in several forms of activity-dependent synaptic plasticity including learning and memory, and stabilization and elimination of synaptic connections during development. Similar molecular mechanisms may underlie plastic changes during development and neuronal destruction by overaction of EAA receptors. A critical level of EAA neurotransmitter activity is required for normal development. However, there appears to be a continuum of physiologic reactions to EAA receptor activation: underactivation can retard or disrupt normal development, whereas overactivation can lead to neuronal injury and destruction (figure 8). The susceptibility of the brain to excitotoxicity is dramatically altered during postnatal development. As a result of these changes, the contribution of NMDA receptor activation in excitotoxic brain injury may be greater during early periods of postnatal development, whereas non-NMDA receptors may make a greater contribution to excitotoxic injury in the adult brain.
McDonald
J W
JW
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Johnston
M V
MV
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity*; D016202:N-Methylaspartate / Q000633:toxicity*; D016318:Quisqualic Acid / Q000633:toxicity*; D017470:Receptors, Glutamate / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; D007608:Kainic Acid