Effect of interferon-³ on parkinsonism and on l-DOPA-induced dyskinesia

• Grant number: 17/14419-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Daniele Pereira Ferrari
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia, AP.TEM
• Associated scholarship(s): 18/18354-7 - Role of the SK3 channel in neuroinflammatory mechanisms of L-DOPA induced-dyskinesia and Parkinson's disease, BE.EP.MS

Abstract

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons whose cause is still unknown. The most effective treatment for PD motor symptoms is through administration of L-DOPA. The chronicity of this treatment leads to the development of abnormal involuntary movements (L-DOPA-induced dyskinesia). In the lesioned striatum of parkinsonian and dyskinetics animals the presence of activated glial cells and increased expression of inducible nitric oxide-synthase (iNOS), suggested the involvement of neuroinflammation in the pathophysiology of PD and dyskinesia. iNOS transcription is dependent on proinflammatory cytokines, including interferon-³ (IFN-³), which apparently participates in the degeneration of dopaminergic neurons. The aim of this study is to extend the analysis of the involvement of inflammatory reaction in dyskinesia by analyzing the role of IFN-³ in Parkinsonism and dyskinesia, as well as the role of IFN-³ in iNOS expression after L-DOPA treatment. For this, we will use IFN-³ knockout (IFN-³-KO) and wild-type (WT) mice for induction of Parkinsonism. They will receive unilateral microinjection of 6-OHDA in the striatum. The intensity of the lesion will be assessed by cylinder test, open field test and later by immunohistochemical analysis for tyrosine hydroxylase in the striatum and substantia nigra of all animals. Lesioned IFN-³-KO and WT animals will be treated with L-DOPA or saline and evaluated for dyskinesia. The presence of inflammatory reaction will be evaluated in the striatum through iNOS expression and microglial activation (IBA-1). The presence of IFN-³ in the serum of WT controls, Parkinsonism and dyskinesia animals will be evaluated by ELISA. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERRARI, D. P.; BORTOLANZA, M.; DEL BEL, E. A.. Interferon-gamma Involvement in the Neuroinflammation Associated with Parkinson's Disease and L-DOPA-Induced Dyskinesia. NEUROTOXICITY RESEARCH, MAR 2021. (14/25029-4, 17/14419-4)

FERRARI, D. P.; BORTOLANZA, M.; DEL BEL, E. A.. Interferon-gamma Involvement in the Neuroinflammation Associated with Parkinson's Disease and L-DOPA-Induced Dyskinesia. NEUROTOXICITY RESEARCH, v. 39, n. 3, p. 15-pg., 2021-03-09. (17/14419-4, 14/25029-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERRARI, Daniele Pereira. Involvement of interferon-γ on Parkinsonism, L-DOPA-induced dyskinesia and expression of neuroinflammatory elements. 2020. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.