| First Author | Leite PE | Year | 2014 |
| Journal | Brain Res | Volume | 1573 |
| Pages | 27-36 | PubMed ID | 24833065 |
| Mgi Jnum | J:309680 | Mgi Id | MGI:6759042 |
| Doi | 10.1016/j.brainres.2014.05.004 | Citation | Leite PE, et al. (2014) Selective activation of alpha7 nicotinic acetylcholine receptor (nAChRalpha7) inhibits muscular degeneration in mdx dystrophic mice. Brain Res 1573:27-36 |
| abstractText | Amount evidence indicates that alpha7 nicotinic acetylcholine receptor (nAChRalpha7) activation reduces production of inflammatory mediators. This work aimed to verify the influence of endogenous nAChRalpha7 activation on the regulation of full-blown muscular inflammation in mdx mouse with Duchenne muscular dystrophy. We used mdx mice with 3 weeks-old at the height myonecrosis, and C57 nAChRalpha7(+/+) wild-type and nAChRalpha7(-/-) knockout mice with muscular injury induced with 60microL 0.5% bupivacaine (bp) in the gastrocnemius muscle. Pharmacological treatment included selective nAChRalpha7 agonist PNU282987 (0.3mg/kg and 1.0mg/kg) and the antagonist methyllycaconitine (MLA at 1.0mg/kg) injected intraperitoneally for 7 days. Selective nAChRalpha7 activation of mdx mice with PNU282987 reduced circulating levels of lactate dehydrogenase (LDH, a marker of cell death by necrosis) and the area of perivascular inflammatory infiltrate, and production of inflammatory mediators TNFalpha and metalloprotease MMP-9 activity. Conversely, PNU282987 treatment increased MMP-2 activity, an indication of muscular tissue remodeling associated with regeneration, in both mdx mice and WTalpha7 mice with bp-induced muscular lesion. Treatment with PNU282987 had no effect on alpha7KO, and MLA abolished the nAChRalpha7 agonist-induced anti-inflammatory effect in both mdx and WT. In conclusion, nAChRalpha7 activation inhibits muscular inflammation and activates tissue remodeling by increasing muscular regeneration. These effects were not accompanied with fibrosis and/or deposition of non-functional collagen. The nAChRalpha7 activation may be considered as a potential target for pharmacological strategies to reduce inflammation and activate mechanisms of muscular regeneration. |
