NADPH DIAPHORASE-CONTAINING STRIATAL OR CORTICAL-NEURONS ARE RESISTANT TO APOPTOSIS

The small subpopulation of striatal neurons containing nicotinamide ad enine dinucleotide phosphate diaphorase (NADPH-d, recently identified as nitric oxide synthase, NOS) is selectively spared in Huntington's d isease. Previous search for pathogenic mechanisms capable of destroyin g striatal neurons but sparing NADPH-d(+) cells has identified only NM DA receptor-mediated excitotoxicity. In view of suggestions that neuro nal death in Huntington's disease may occur by apoptosis, we examined the vulnerability of NADPH-d(+) neurons to apoptosis. Murine striatal or cortical cultures exposed to serum deprivation developed extensive neuronal apoptosis, but NADPH-d(+) neurons were relatively spared. Thi s sparing was seen when cultures were exposed to several other apoptos is-inducing insults. It was not seen after toxic exposure to H2O2, and it was not blocked by NOS inhibition. The selective resistance of NAD PH-d(+) neurons to several forms of apoptosis provides key support for the possibility that apoptosis may contribute to the pathogenesis of Huntington's disease. (C) 1996 Academic Press, Inc.