Effects of the mineralocorticoid receptor antagonist eplerenone in experimental autoimmune encephalomyelitis.
J Steroid Biochem Mol Biol
; 238: 106461, 2024 04.
Article
in En
| MEDLINE
| ID: mdl-38219844
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-ß-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-1ß, and iNOS mRNAs; (b) attenuated HMGB1, NLRP3, TGF-ß mRNAs, microglia, and aquaporin4 immunoreaction without modifying GFAP. Serum IL-1ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Encephalomyelitis, Autoimmune, Experimental
Limits:
Animals
Language:
En
Journal:
J Steroid Biochem Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: