Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis Development in Mice

Molecular Neurobiology
Vicente LieberknechtRafael C Dutra

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 ...Continue Reading

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Citations

Jan 13, 2018·International Journal of Molecular Sciences·Manish K Jha, Madhukar H Trivedi
Apr 24, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Mikhail MelnikovMikhail Pashenkov
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Mar 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ya-Shuo FengFeng Zhang
Mar 18, 2021·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·M V MelnikovA N Boyko
Apr 27, 2021·Frontiers in Immunology·Yifei Feng, Yan Lu
Jun 3, 2021·International Journal of Molecular Sciences·Mikhail MelnikovAlexey Boyko
Jul 17, 2021·Neural Regeneration Research·Carlos Pereira MartinsRafael Cypriano Dutra
Aug 26, 2021·Molecular Neurobiology·E C D GonçalvesR C Dutra

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

NIH ImageJ
GraphPad Prism
GraphPad
Image Lab

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