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Open AccessFeature PaperArticle

Attenuation in Nicotinic Acetylcholine Receptor α9 and α10 Subunit Double Knock-Out Mice of Experimental Autoimmune Encephalomyelitis

1
Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA
2
Boys Town National Research Hospital, Omaha, NE 68131, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 827; https://doi.org/10.3390/biom9120827
Received: 25 October 2019 / Revised: 15 November 2019 / Accepted: 24 November 2019 / Published: 4 December 2019
Experimental autoimmune encephalomyelitis (EAE) is attenuated in nicotinic acetylcholine receptor (nAChR) α9 subunit knock-out (α9 KO) mice. However, protection is incomplete, raising questions about roles for related, nAChR α10 subunits in ionotropic or recently-revealed metabotropic contributions to effects. Here, we demonstrate reduced EAE severity and delayed onset of disease signs in nAChR α9/α10 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 α9 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 α9 subunits. These findings minimize the likelihood that additional deletion of nAChR α10 subunits impacts disease differently than α9 KO alone, whether through ionotropic, metabotropic, or alternative mechanisms. Moreover, our results provide further evidence of disease-exacerbating roles for nAChR containing α9 subunits (α9*-nAChR) in EAE inflammatory and autoimmune responses. This supports our hypothesis that α9*-nAChR or their downstream mediators are attractive targets for attenuation of inflammation and autoimmunity.
Keywords: autoimmunity; cholinergic anti-inflammatory pathway; experimental autoimmune encephalomyelitis; inflammation; multiple sclerosis; nicotinic acetylcholine receptors autoimmunity; cholinergic anti-inflammatory pathway; experimental autoimmune encephalomyelitis; inflammation; multiple sclerosis; nicotinic acetylcholine receptors
MDPI and ACS Style

Liu, Q.; Li, M.; Whiteaker, P.; Shi, F.-D.; Morley, B.J.; Lukas, R.J. Attenuation in Nicotinic Acetylcholine Receptor α9 and α10 Subunit Double Knock-Out Mice of Experimental Autoimmune Encephalomyelitis. Biomolecules 2019, 9, 827.

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