title: Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats.
abstract: 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.
authors.affiliation: International Center for Neurological Restoration (CIREN), Havana, Cuba. Electronic address: mldiaz@neuro.ciren.cu.
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Díaz-Hung
authors.affiliation: Pharmaceutics Biological Laboratories (LABIOFAM), Havana, Cuba.
authors.forename: Arianna
authors.initials: A
authors.lastname: Yglesias-Rivera
authors.affiliation: Research Department, Asociación para Evitar la Ceguera "Hospital Luis Sanchez Bulnes", IAP. México City 04030, Mexico.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Hernández-Zimbrón
authors.affiliation: Specialty Hospital from Neurological Diseases, CMN, SXXI, IMSS, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orozco-Suárez
authors.affiliation: Tropical Medicine 'Pedro Kourí' Institute (IPK), Havana, Cuba.
authors.forename: Jenny Laura
authors.initials: JL
authors.lastname: Ruiz-Fuentes
authors.affiliation: Pharmaceutics Biological Laboratories (LABIOFAM), Havana, Cuba.
authors.forename: Alexis
authors.initials: A
authors.lastname: Díaz-García
authors.affiliation: International Center for Neurological Restoration (CIREN), Havana, Cuba.
authors.forename: Rilda
authors.initials: R
authors.lastname: León-Martínez
authors.affiliation: International Center for Neurological Restoration (CIREN), Havana, Cuba.
authors.forename: Lisette
authors.initials: L
authors.lastname: Blanco-Lezcano
authors.affiliation: International Center for Neurological Restoration (CIREN), Havana, Cuba.
authors.forename: Nancy
authors.initials: N
authors.lastname: Pavón-Fuentes
authors.affiliation: International Center for Neurological Restoration (CIREN), Havana, Cuba.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Lorigados-Pedre
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019328:Buthionine Sulfoximine; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione
keywords: cytokines; glutathione; microglia; neuroinflammation; nitric oxide; substantia nigra