Basal forebrain cholinergic neurons are selectively vulnerable to AMPA/kainate receptor-mediated neurotoxicity.
We exposed murine basal forebrain neuronal cultures for 24 h to defined concentrations of N-methyl-D-aspartate, kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and assessed the resultant degeneration of the cholinergic neuronal subpopulation, as identified by choline acetyltransferase immunocytochemistry and acetylcholinesterase histochemistry. Cholinergic neurons, representing about 0.5% of the total neuronal population, were atypically vulnerable to excitotoxins. Compared to most basal forebrain neurons, they were more vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor-mediated injury and slightly less vulnerable to N-methyl-D-aspartate receptor-mediated injury. The present findings provide quantitative demonstration of a mechanism that preferentially injures basal forebrain cholinergic neurons, and may thus suggest candidate factors pertaining to their loss in disease states like Alzheimer's disease.
Weiss
J H
JH
Department of Neurology, University of California, Irvine 92717.
Yin
H Z
HZ
Choi
D W
DW
D000109:Acetylcholine; D000110:Acetylcholinesterase / Q000032:analysis; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000032:analysis; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D018091:Receptors, AMPA / Q000187:drug effects* / Q000502:physiology; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D000109:Acetylcholine; D000110:Acetylcholinesterase; D002795:Choline O-Acetyltransferase; D007608:Kainic Acid; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid