1. Effects of the mineralocorticoid receptor antagonist eplerenone in experimental autoimmune encephalomyelitis.
- Author
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Alvarez Quintero GS, Lima A, Roig P, Meyer M, de Kloet ER, De Nicola AF, and Garay LI
- Subjects
- Mice, Animals, Eplerenone pharmacology, Eplerenone therapeutic use, Mineralocorticoid Receptor Antagonists pharmacology, Mineralocorticoid Receptor Antagonists therapeutic use, Neuroinflammatory Diseases, Spinal Cord pathology, Mice, Inbred C57BL, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental metabolism
- Abstract
There is growing evidence indicating that mineralocorticoid receptor (MR) expression influences a wide variety of functions in metabolic and immune response. The present study explored if antagonism of the MR reduces neuroinflammation in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). Eplerenone (EPLE) (100 mg/kg dissolved in 30% 2-hydroxypropyl-β-cyclodextrin) was administered intraperitoneally (i.p.) daily from EAE induction (day 0) until sacrificed on day 17 post-induction. The MR blocker (a) significantly decreased the inflammatory parameters TLR4, MYD88, IL-1β, and iNOS mRNAs; (b) attenuated HMGB1, NLRP3, TGF-β mRNAs, microglia, and aquaporin4 immunoreaction without modifying GFAP. Serum IL-1β was also decreased in the EAE+EPLE group. Moreover, EPLE treatment prevented demyelination and improved clinical signs of EAE mice. Interestingly, MR was decreased and GR remained unchanged in EAE mice while EPLE treatment restored MR expression, suggesting that a dysbalanced MR/GR was associated with the development of neuroinflammation. Our results indicated that MR blockage with EPLE attenuated inflammation-related spinal cord pathology in the EAE mouse model of Multiple Sclerosis, supporting a novel therapeutic approach for immune-related diseases., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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