| First Author | Liu Q | Year | 2019 |
| Journal | Biomolecules | Volume | 9 |
| Issue | 12 | PubMed ID | 31817275 |
| Mgi Jnum | J:296534 | Mgi Id | MGI:6467909 |
| Doi | 10.3390/biom9120827 | Citation | Liu Q, et al. (2019) Attenuation in Nicotinic Acetylcholine Receptor alpha9 and alpha10 Subunit Double Knock-Out Mice of Experimental Autoimmune Encephalomyelitis. Biomolecules 9(12):827 |
| abstractText | Experimental autoimmune encephalomyelitis (EAE) is attenuated in nicotinic acetylcholine receptor (nAChR) alpha9 subunit knock-out (alpha9 KO) mice. However, protection is incomplete, raising questions about roles for related, nAChR alpha10 subunits in ionotropic or recently-revealed metabotropic contributions to effects. Here, we demonstrate reduced EAE severity and delayed onset of disease signs in nAChR alpha9/alpha10 subunit double knock-out (DKO) animals relative to effects in wild-type (WT) control mice. These effects are indistinguishable from contemporaneously-observed effects in nicotine-treated WT or in alpha9 KO mice. Immune cell infiltration into the spinal cord and brain, reactive oxygen species levels in vivo, and demyelination, mostly in the spinal cord, are reduced in DKO mice. Disease severity is not altered relative to WT controls in mice harboring a gain-of-function mutation in alpha9 subunits. These findings minimize the likelihood that additional deletion of nAChR alpha10 subunits impacts disease differently than alpha9 KO alone, whether through ionotropic, metabotropic, or alternative mechanisms. Moreover, our results provide further evidence of disease-exacerbating roles for nAChR containing alpha9 subunits (alpha9*-nAChR) in EAE inflammatory and autoimmune responses. This supports our hypothesis that alpha9*-nAChR or their downstream mediators are attractive targets for attenuation of inflammation and autoimmunity. |
