DEATH OF SUBCORTICAL CHOLINERGIC NEURONS IN CERTAIN NEURODEGENERATIVE DISORDERS MAY NOT BE DUE TO AN OVERSTIMULATION OF N-METHYL-D-ASPARTATE RECEPTORS

Stimulation of N-methyl-d-aspartate (NMDA) receptors increases the activity of enzymes involved in the synthesis of nerve cell specific neurotransmitters. In the present study this phenomenon has been used to identify the neurons in the septal-diagonal band region having NMDA receptors. Exposure of cultures relatively enriched in subcortical cholinergic neurons to a depolarizing concentration of K+ (40 mM) significantly enhanced the expression of choline acetyltransferase (ChAT) activity. In contrast, when these septal cells were treated with as much as 100 μM NMDA no significant increase was observed in the activity of choline acetyltransferase, although there was a marked enhancement in glutamate decarboxylase activity. The results would indicate that subcortical cholinergic neurons do not possess excitatory amino acid receptors of the NMDA subtype, and that therefore neurotoxicity mediated through NMDA receptors may not be involved in the death of cholinergic neurons in degenerative disorders of the brain, such as Down's syndrome and Alzheimer's disease, which entail major losses of these neurons. © 1990.