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

Author(s)

Ferrari, D. P. ; Bortolanza, M. ; Del Bel, E. A.

• Document type: Journal article
• Source: NEUROTOXICITY RESEARCH; v. 39, n. 3, p. 15-pg., 2021-03-09.

Abstract

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)

• FAPESP's process: 17/14419-4 - Effect of interferon-³ on parkinsonism and on l-DOPA-induced dyskinesia
• Grantee: Daniele Pereira Ferrari
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia
• Grantee: Elaine Aparecida Del Bel Belluz Guimarães
• Support Opportunities: Research Projects - Thematic Grants