Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration
| Autor: | Cecília Cerqueira Café-Mendes, Luiz R.G. Britto, Larissa de Sá Lima, Marina S. Hernandes, Graziella D. R. Santos, Carolina Demarchi Munhoz, Cristoforo Scavone |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Apomorphine lcsh:Medicine Minocycline Striatum chemistry.chemical_compound Mice NADH NADPH Oxidoreductases lcsh:Science Mice Knockout Multidisciplinary Membrane Glycoproteins Microglia Neurodegeneration Dopaminergic NF-kappa B Parkinson Disease Substantia Nigra medicine.anatomical_structure NOX1 Knockout mouse NADPH Oxidase 2 NADPH Oxidase 1 cardiovascular system Oxidopamine Research Article medicine.medical_specialty animal structures Substantia nigra Biology FARMACOLOGIA Internal medicine medicine Animals Inflammation Tumor Necrosis Factor-alpha Dopaminergic Neurons lcsh:R NADPH Oxidases medicine.disease Corpus Striatum Mice Inbred C57BL Disease Models Animal Endocrinology chemistry nervous system Immunology Nerve Degeneration lcsh:Q |
| Zdroj: | PLoS ONE, Vol 8, Iss 9, p e75532 (2013) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | We explored the impact of Nox-2 in modulating inflammatory-mediated microglial responses in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model. Nox1 and Nox2 gene expression were found to increase in striatum, whereas a marked increase of Nox2 expression was observed in substantia nigra (SN) of wild-type (wt) mice after PD induction. Gp91(phox-/-) 6-OHDA-lesioned mice exhibited a significant reduction in the apomorphine-induced rotational behavior, when compared to wt mice. Immunolabeling assays indicated that striatal 6-OHDA injections reduced the number of dopaminergic (DA) neurons in the SN of wt mice. In gp91(phox-/-) 6-OHDA-lesioned mice the DA degeneration was negligible, suggesting an involvement of Nox in 6-OHDA-mediated SN degeneration. Gp91(phox-/-) 6-OHDA-lesioned mice treated with minocycline, a tetracycline derivative that exerts multiple anti-inflammatory effects, including microglial inhibition, exhibited increased apomorphine-induced rotational behavior and degeneration of DA neurons after 6-OHDA injections. The same treatment also increased TNF-α release and potentiated NF-κB activation in the SN of gp91(phox-/-)-lesioned mice. Our results demonstrate for the first time that inhibition of microglial cells increases the susceptibility of gp91(phox-/-) 6-OHDA lesioned mice to develop PD. Blockade of microglia leads to NF-κB activation and TNF-α release into the SN of gp91(phox-/-) 6-OHDA lesioned mice, a likely mechanism whereby gp91(phox-/-) 6-OHDA lesioned mice may be more susceptible to develop PD after microglial cell inhibition. Nox2 adds an essential level of regulation to signaling pathways underlying the inflammatory response after PD induction. |
| Databáze: | OpenAIRE |
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