Estrogen inhibits estrogen receptor α-mediated rho-kinase expression in experimental autoimmune encephalomyelitis rats
Version of Record online: 25 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 7, pages 399–406, July 2013
How to Cite
Feng, J., Zhang, G., Hu, X., Si Chen, C. and Qin, X. (2013), Estrogen inhibits estrogen receptor α-mediated rho-kinase expression in experimental autoimmune encephalomyelitis rats. Synapse, 67: 399–406. doi: 10.1002/syn.21650
- Issue online: 15 MAY 2013
- Version of Record online: 25 MAR 2013
- Accepted manuscript online: 9 FEB 2013 12:00AM EST
- Manuscript Accepted: 6 FEB 2013
- Manuscript Revised: 5 FEB 2013
- Manuscript Received: 11 SEP 2012
- multiple sclerosis;
- experimental autoimmune encephalomyelitis;
- estrogen receptor α
The anti-inflammatory and neuroprotective effects of estrogen on multiple sclerosis (MS) have been reported in previous studies. Evidence has been found that estrogen can inhibit axonal loss in the MOG-induced experimental autoimmune encephalomyelitis (EAE) model of MS. Rho-kinase (ROCK) mediates axonal growth-inhibitory signals via the Rho/Rho-kinase pathway. The inhibition of ROCK decreases axonal loss in EAE. However, there is no study reporting the association between estrogen and ROCK in MS and EAE. We examined the anti-inflammatory and axonal protective effects of estrogen and explored the probable mechanism whereby estrogen inhibits ROCK through ERα in EAE rats. Results show that 17β-estradiol (E2) can significantly avoid the loss of neurological function in EAE rats. E2 also decreased the infiltration of inflammatory cells and cytokines including IL-1β, TNF-α, and IL-17, but increased the expression of IL-4. E2 inhibited the expression of ROCK and NF-200 in EAE rats. The inhibitory effect on ROCK was abolished when nonselective estrogen receptor (ER) antagonist ICI 182780 was added to E2. Furthermore, the expression of ROCK was inhibited by ERα-selective ligand agonist propyl pyrazole triol. ERβ-selective ligand WAY-202041 has no effect on the expression of ROCK. These observations suggest that estrogen inhibits the expression of ROCK in EAE rats and that the inhibitory effects are mediated by ERα rather than ERβ. Synapse 67:399–406, 2013. © 2013 Wiley Periodicals, Inc.