Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats

• The present data show that transient glutathione depletion causes:
• Cellular death in the substantia nigra pars compacta.
• Microglia recruitment and increased levels of proinflammatory cytokines.
• Early activation of c-Jun N-terminal kinase.
• Activation of inducible nitric oxide synthase and nitric oxide production.

Glutathione (GSH) deficiency has been identified as an early event in the progression of Parkinson’s disease. However, the role of GSH in the etiology and pathogenesis of this neurodegenerative disorder is not well established. The aim of this study is to assess the effect of transient GSH depletion in the substantia nigra pars compacta (SNpc) on neuroinflammation after the injection of a single dose of l-buthionine sulfoximine (BSO) into the SNpc of male Sprague–Dawley rats. The results showed that BSO treatment stimulates microglia (p < 0.01) and astroglial response (p < 0.01), c-Jun N-terminal kinase and inducible nitric oxide synthase (iNOS) (p < 0.001) in the SNpc, accompanied by dopaminergic dysfunction. In addition, high levels of tumor necrosis factor α (p < 0.01), interleukins IL-1β p < 0.01), IL-6 p < 0.001) and nitric oxide p < 0.01) were found in the treated animals compared to control groups, while no significant differences were found in IL-10 levels. These results suggest that transient GSH depletion can increase the susceptibility of SNpc to degeneration by promoting an inflammatory response and nitrosative stress, reinforcing the possible role of GSH unbalance, oxygen/nitrogen reactive species and neuroinflammation as causal factors on the degeneration of the SNpc.

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