Cultured striatal neurons containing NADPH-diaphorase or acetylcholinesterase are selectively resistant to injury by NMDA receptor agonists.

Cultured striatal neurons containing either NADPH-diaphorase or acetylcholinesterase were more resistant to injury by N-methyl-D-aspartate (NMDA) or quinolinate, than the general striatal neuronal population, although this resistance was not absolute and could be overcome by intense toxic exposure. Neurons containing NADPH-diaphorase, but not neurons containing acetylcholinesterase, also exhibited heightened vulnerability to injury by kainate. Given recent evidence that diaphorase- and cholinesterase-containing striatal neurons are selectively spared in Huntington's disease, our results strengthen the possibility that NMDA receptor-mediated neurotoxicity may participate in the pathogenesis of that disease.