title: NADPH oxidase and the degeneration of dopaminergic neurons in parkinsonian mice.
abstract: Several lines of investigation have implicated oxidative stress in Parkinson's disease (PD) pathogenesis, but the mechanisms involved are still unclear. In this study, we characterized the involvement of NADPH oxidase (Nox), a multisubunit enzyme that catalyzes the reduction of oxygen, in the 6-hydroxydopamine- (6-OHDA-) induced PD mice model and compared for the first time the effects of this neurotoxin in mice lacking gp91(phox-/-), the catalytic subunit of Nox2, and pharmacological inhibition of Nox with apocynin. Six-OHDA induced increased protein expression of p47(phox), a Nox subunit, in striatum. gp91(phox-/-) mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited neuroprotection. Wt mice treated with apocynin and gp91(phox-/-) mice both exhibited ameliorated apomorphine-induced rotational behavior. The microglial activation observed within the striatum and the substantia nigra pars compacta (SNpc) of 6-OHDA-injected Wt mice was prevented by apocynin treatment and was not detected in gp91(phox-/-) mice. Apocynin was not able to attenuate astrocyte activation in SN. The results support a role for Nox2 in the 6-OHDA-induced degeneration of dopaminergic neurons and glial cell activation in the nigrostriatal pathway and reveal that no comparable 6-OHDA effects were observed between apocynin-treated and gp91(phox-/-) mice groups.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900 SP, Brazil.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Hernandes
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900 SP, Brazil.
authors.forename: Cecília C
authors.initials: CC
authors.lastname: Café-Mendes
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900 SP, Brazil.
authors.forename: Luiz R G
authors.initials: LR
authors.lastname: Britto
mesh_terms: D000818:Animals; D001058:Apomorphine; D039481:CD11b Antigen / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D017072:Neostriatum / Q000201:enzymology / Q000473:pathology; D009410:Nerve Degeneration / Q000201:enzymology* / Q000473:pathology*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology*; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D001058:Apomorphine