Attenuation in nicotinic acetylcholine receptor α9 and α10 subunit double knock-out mice of experimental autoimmune encephalomyelitis

Qiang Liu, Minshu Li, Paul Whiteaker, Fu Dong Shi, Barbara J. Morley, Ronald J. Lukas

Research output: Contribution to journalArticle

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Abstract

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 recentlyrevealed 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.

Original languageEnglish (US)
Article number827
JournalBiomolecules
Volume9
Issue number12
DOIs
StatePublished - Dec 2019

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Keywords

  • Autoimmunity
  • Cholinergic anti-inflammatory pathway
  • Experimental autoimmune encephalomyelitis
  • Inflammation
  • Multiple sclerosis
  • Nicotinic acetylcholine receptors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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