Excitotoxin-mediated neuron death in youth and old age.
Here I have discussed current issues in excitotoxicology (neurotoxicity of Glu and related agents) with special emphasis on the NMDA receptor and its possible role in neuropsychiatric disorders. I have briefly described several classes of anti-excitotoxic agents which are currently under study for their ability to protect neurons against excitotoxin-mediated neuronal degeneration. There is growing interest in the possibility that such agents, especially NMDA antagonists will prove useful in the clinical management of neurodegenerative disorders; however, neither their efficacy nor safety has been adequately established at present. With the plethora of new information about the NMDA receptor--ionophore complex, one tends to forget that non-NMDA receptors can also mediate excitotoxic events. Thus, although we know less about the physiology and make up of non-NMDA receptors, it seems likely that new information, as it becomes available, will reveal new links between endogenous excitotoxins and neuropsychiatric disease processes. In particular, since NMDA receptors are relatively more sensitive in early life and non-NMDA receptors more sensitive in adulthood, it is reasonable to postulate the greatest involvement of the former in developmental psychoneuropathology and the latter in neurodegenerative diseases of the elderly.
Olney
J W
JW
Department of Psychiatry, Washington University Medical School, St. Louis, MO 63110.
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000502:physiology; D001928:Brain Diseases, Metabolic / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology; D015220:Calcium Channels / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development / Q000293:injuries; D002493:Central Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D005502:Food / Q000009:adverse effects; D005503:Food Additives / Q000009:adverse effects; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology
D000596:Amino Acids; D015220:Calcium Channels; D005503:Food Additives; D005971:Glutamates; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid