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Published on: September 9, 2022
Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis
Vicente Lieberknecht1,2,3, Stella C Junqueira1,2, Mauricio P Cunha3
1Laboratory 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.
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.
Insights
Pramipexole (PPX), a dopamine agonist, effectively prevented experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). PPX treatment blocked neuroinflammation and demyelination, suggesting its therapeutic potential for MS and related inflammatory diseases.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a key animal model for multiple sclerosis (MS) research.
- Dopamine receptors influence EAE and MS pathogenesis, indicating potential therapeutic roles for dopaminergic agonists.
- The therapeutic application of dopaminergic agonists in MS remains underexplored.
Purpose of the Study:
- To investigate the efficacy of pramipexole (PPX), a dopamine D2/D3 receptor agonist, in preventing EAE.
- To elucidate the underlying mechanisms of PPX action in the context of EAE.
Main Methods:
- PPX was administered intraperitoneally at 0.1 and 1 mg/kg from day 0 to 40 post-immunization in EAE models.
- Evaluated EAE clinical signs, neuroinflammation, demyelination, and astroglial activation in the spinal cord.
- Assessed inflammatory cytokine production in peripheral lymphoid tissues and molecular changes in spinal cord and striatum.
Main Results:
- PPX at 1 mg/kg significantly prevented EAE development and abolished clinical signs.
- PPX treatment blocked spinal cord neuroinflammation, demyelination, and astroglial activation.
- PPX inhibited pro-inflammatory cytokines (IL-17, IL-1β, TNF-α) and restored molecular markers in the spinal cord and striatum.
Conclusions:
- PPX demonstrates significant therapeutic potential in preventing EAE, a model for MS.
- PPX acts by modulating neuroinflammatory responses, demyelination, and immune cell activity.
- These findings suggest PPX could be a valuable treatment for MS and other T helper cell-mediated inflammatory diseases.
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