GLUTATHIONE DEPLETION IN RAT-BRAIN DOES NOT CAUSE NIGROSTRIATAL PATHWAY DEGENERATION

Nigral cell death in Parkinson's disease (PD) may involve oxidative st ress and mitochondrial dysfunction initiated by a decrease in reduced glutathione (GSH) levels in substantia nigra. L-buthionine-(S,R)-sulph oximine (BSO; 4.8 and 9.6 mg/kg/day), an irreversible inhibitor of gam ma-glutamyl cysteine synthetase, was chronically infused into the left lateral ventricle of rats over a period of 28 days and markedly reduc ed GSH concentrations in substantia nigra (approx. 59% and 65% in 4.8 and 9.6 mg/kg/d BSO respectively) and the striatum (approx. 63% and 80 % in 4.8 and 9.6mg/kg/d BSO respectively). However, the number of tyro sine hydroxylase (TH)-positive cells in substantia nigra was not alter ed by BSO-treatment compared to control animals. Similarly, there was no difference in specific [H-3]-mazindol binding in the striatum and n ucleus accumbens of BSO-treated rats compared to control rats. In conc lusion, depletion of GSH following chronic administration of BSO in th e rat brain does not cause damage to the nigrostriatal pathway and sug gests that loss of GSH alone is not responsible for nigrostriatal dama ge in PD. Rather, GSH depletion may enhance the susceptibility of subs tantia nigra to destruction by endogenous or exogenous toxins.