Nigrostriatal dopaminergic neurotoxicity of L-cysteine after stereotaxic administration into the substantia nigra of rats: Potential implications for MPTP-induced neurotoxicity and parkinson’s disease

Abstract

Stereotaxic administration of L-cysteine (CySH) into the rat substantia nigra pars compacta (SN c) evokes a dose-dependent fall of striatal levels of dopamine. This, together with decreased tyrosine hydroxylase immunoreactivity in the striatum and SNcand decreased nigral staining for Nissl substance indicate that CySH is a dopaminergic neurotoxin. The neurotoxic effects of CySH infusion into the rat SN c were blocked by prior administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Previous studies have demonstrated that administration of the neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) not only evokes the degeneration of nigrostriatal dopamine neurons but also causes a significant fall of glutathione (GSH) without corresponding increases of glutathione disulfide (GSSG). Furthermore, microdialysis studies have demonstrated that when perfusions of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of MPTP, into the rat SN c are discontinued extracellular levels of GSH massively but transiently increase followed by a prolonged elevation of extracellular CySH, the latter effect being blocked by inhibition of ~/-glutamyl. transpeptidase (~/-GT). These observations, together with the present results, suggest that the delayed but prolonged elevation of extracellular CySH that occurs as a MPP+-induced dopaminergic SNccell energy impairment begins to subside might evoke NMDA receptor mediated excitotoxicity. The potential roles of elevated extracellular CySH in MPTP/MPP+-induced dopaminergic neurotoxicity and in the pathogenesis of Parkinson's disease are discussed.

Revisiting the systemic lipopolysaccharide mediated neuroinflammation: Appraising the effect of l -cysteine mediated hydrogen sulphide on it

“…Considering the above H 2 S donors are nowadays suggested/evaluated in various pathologies and on the same line l -cysteine has been evaluated in variable preclinical setups. Nonetheless there are variable reports with few citing it is neurotoxic and some favoring it as neuroprotective (Gu et al, 2000, Janaky, et al, 2000, Hashimoto et al, 2004)…”

Review on apoptosis vs. necrosis of substantia nigrapars compacta in parkinson’s disease

“…Protein-catechol conjugates are detectable and evident signs of neurotoxicity (Hastings and Zigmond, 1994;Hastings et al, 1996). Also, L-cysteine per se is neurotoxic in high concentrations, and has been implicated as a mediator of nigral toxicity in Parkinson's disease (PD) (Gu et al, 2000).…”