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Interferon-gamma Involvement in the Neuroinflammation Associated with Parkinson's Disease and L-DOPA-Induced Dyskinesia

Texto completo
Autor(es):
Ferrari, D. P. [1, 2] ; Bortolanza, M. [2] ; Del Bel, E. A. [1, 2]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Neurosci, BR-14040900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, BR-14040904 Sao Paulo, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: NEUROTOXICITY RESEARCH; MAR 2021.
Citações Web of Science: 0
Resumo

Interferon-gamma (IFN-gamma) is a proinflammatory cytokine that activates glial cells. IFN-gamma is increased in the plasma and brain of Parkinson's disease patients, suggesting its potential role in the disease. We investigated whether the IFN-gamma deficiency could interfere with nigrostriatal degeneration induced by the neurotoxin 6-hydroxydopamine, L-DOPA-induced dyskinesia, and the neuroinflammatory features as astrogliosis, microgliosis, and induced nitric oxide synthase (iNOS) immunoreactivity induced by L-DOPA treatment. Wild type (WT) and IFN-gamma knockout (IFN-gamma/KO) mice received unilateral striatal microinjections of 6-hydroxydopamine. Animals were sacrificed 1, 3, 7, and 21 days after lesions. Additional group of WT and IFN-gamma/KO parkinsonian mice, after 3 weeks of neurotoxin injection, received L-DOPA (intraperitoneally, for 21 days) resulting in dyskinetic-like behavior. Tyrosine hydroxylase immunostaining indicated the starting of dopaminergic lesion since the first day past toxin administration, progressively increased until the third day when it stabilized. There was no difference in the lesion and L-DOPA-induced dyskinesia intensity between WT and IFN-gamma/KO mice. Remarkably, IFN-gamma/KO mice treated with L-DOPA presented in the lesioned striatum an increase of iNOS and glial fibrilary acid protein (GFAP) density, compared with the WT group. Morphological analysis revealed the rise of astrocytes and microglia reactivity in IFN-gamma/KO mice exibiting dyskinesia. In conclusion, IFN-gamma/KO mice presented an intensification of the inflammatory reaction accompanying L-DOPA treatment and suggest that iNOS and GFAP increase, and the activation of astrocytes and microglia induced afterward L-DOPA treatment was IFN-gamma independent events. Intriguingly, IFN-gamma absence did not affect the degeneration of dopaminergic neurons or LID development. (AU)

Processo FAPESP: 14/25029-4 - Estudo da contribuição do processo inflamatório na discinesia induzida por L-DOPA na Doença de Parkinson
Beneficiário:Elaine Aparecida Del Bel Belluz Guimarães
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/14419-4 - Efeito do interferon-³ sobre o parkinsonismo e no desenvolvimento de discinesia induzida pelo tratamento com L-DOPA
Beneficiário:Daniele Pereira Ferrari
Linha de fomento: Bolsas no Brasil - Mestrado