title: Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis Development in Mice.
abstract: Experimental autoimmune encephalomyelitis (EAE) is the most used animal model of multiple sclerosis (MS) for the development of new therapies. Dopamine receptors can modulate EAE and MS development, thus highlighting the potential use of dopaminergic agonists in the treatment of MS, which has been poorly explored. Herein, we hypothesized that pramipexole (PPX), a dopamine D2/D3 receptor-preferring agonist commonly used to treat Parkinson's disease (PD), would be a suitable therapeutic drug for EAE. Thus, we report the effects and the underlying mechanisms of action of PPX in the prevention of EAE. PPX (0.1 and 1 mg/kg) was administered intraperitoneally (i.p.) from day 0 to 40 post-immunization (p.i.). Our results showed that PPX 1 mg/kg prevented EAE development, abolishing EAE signs by blocking neuroinflammatory response, demyelination, and astroglial activation in spinal cord. Moreover, PPX inhibited the production of inflammatory cytokines, such as IL-17, IL-1β, and TNF-α in peripheral lymphoid tissue. PPX was also able to restore basal levels of a number of EAE-induced effects in spinal cord and striatum, such as reactive oxygen species, glutathione peroxidase, parkin, and α-synuclein (α-syn). Thus, our findings highlight the usefulness of PPX in preventing EAE-induced motor symptoms, possibly by modulating immune cell responses, such as those found in MS and other T helper cell-mediated inflammatory diseases.
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, Rodovia Jorge Lacerda, Km 35,4, Jardim das Avenidas, 88906-072, Araranguá, SC, Brazil.|Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.|Department of Biochemistry, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lieberknecht
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, Rodovia Jorge Lacerda, Km 35,4, Jardim das Avenidas, 88906-072, Araranguá, SC, Brazil.|Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Stella C
authors.initials: SC
authors.lastname: Junqueira
authors.affiliation: Department of Biochemistry, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Cunha
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, Rodovia Jorge Lacerda, Km 35,4, Jardim das Avenidas, 88906-072, Araranguá, SC, Brazil.
authors.forename: Thaís A
authors.initials: TA
authors.lastname: Barbosa
authors.affiliation: Department of Biochemistry, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: de Souza
authors.affiliation: Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.|Neurobiology Laboratory of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Coelho
authors.affiliation: Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.|Neurobiology Laboratory of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.|Department of Biochemistry, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.affiliation: Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.|Department of Biochemistry, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafré
authors.affiliation: Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, Rodovia Jorge Lacerda, Km 35,4, Jardim das Avenidas, 88906-072, Araranguá, SC, Brazil. rafaelcdutra@gmail.com.|Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil. rafaelcdutra@gmail.com.
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Dutra
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000276:immunology; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000276:immunology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole
keywords: Autoimmunity; Dopamine receptor agonist; Experimental autoimmune encephalomyelitis; Pramipexole