MESENCEPHALIC NEURON DEATH INDUCED BY CONGENERS OF NITROGEN MONOXIDE IS PREVENTED BY THE LAZAROID U-83836E

We explored the effects of congeners of nitrogen monoxide (NO) on cult ured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a d onor of NO, the congeners of which have been found to exert either neu rotoxic or neuroprotective effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitros onium ion (NO+) is neuroprotective to cultured cortical neurons, we fo und that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment o f dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric ox ide radi cal (NO.) had presumably been formed. We also evaluated the e ffects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, a gainst SNP toxicity. U-83836E exerted marked neuroprotective effects i n both insult models. More than twice as many dopamine neurons (75% of control) survived when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U- 83836E was added to cultures treated with SNP plus ascorbate. We concl ude that the congeners of NO released by SNP are toxic to mesencephali c neurons in vitro and that the lazaroid U-83836E significantly increa ses the survival of dopamine neurons in situations where congeners of NO are generated.