Glutathione depletion in rat brain does not cause nigrostriatal pathway degeneration

被引:75
作者
Toffa, S
Kunikowska, GM
Zeng, BY
Jenner, P
Marsden, CD
机构
[1] UNIV LONDON KINGS COLL, DIV BIOMED SCI, PHARMACOL GRP, NEURODEGENERAT DIS RES CTR, LONDON WC2R 2LS, ENGLAND
[2] ROYAL FREE HOSP, SCH MED, UNIV DEPT SURG, LONDON, ENGLAND
[3] NATL HOSP NEUROL & NEUROSURG, INST NEUROL, UNIV DEPT CLIN NEUROL, LONDON WC1N 3BG, ENGLAND
基金
英国惠康基金;
关键词
Parkinson's disease; reduced glutathione (GSH); oxidative stress; nigrostriatal pathway; L-buthionine sulphoximine (BSO); L-BUTHIONINE SULFOXIMINE; PARKINSONS-DISEASE; LEWY BODY; DEFICIENCY; DOPAMINE;
D O I
10.1007/BF01271295
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Nigral cell death in Parkinson's disease (PD) may involve oxidative stress and mitochondrial dysfunction initiated by a decrease in reduced glutathione (GSH) levels in substantia nigra. L-buthionine-(S,R)-sulphoximine (BSO; 4.8 and 9.6 mg/kg/day), an irreversible inhibitor of gamma-glutamyl cysteine synthetase, was chronically infused into the left lateral ventricle of rats over a period of 28 days and markedly reduced 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 tyrosine hydroxylase (TH)-positive cells in substantia nigra was not altered by BSO-treatment compared to control animals. Similarly, there was no difference in specific [H-3]-mazindol binding in the striatum and nucleus accumbens of BSO-treated rats compared to control rats. In conclusion, depletion of GSH following chronic administration of BSO in the rat brain does not cause damage to the nigrostriatal pathway and suggests that loss of GSH alone is not responsible for nigrostriatal damage in PD. Rather, GSH depletion may enhance the susceptibility of substantia nigra to destruction by endogenous or exogenous toxins.
引用
收藏
页码:67 / 75
页数:9
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