title: The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components.
abstract: Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS) and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the experimental autoimmune encephalomyelitis (EAE) model, and have explored their underlying mechanism of action. Our results show that nicotine ameliorates the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE, and we identify a particular cigarette smoke compound, acrolein, as one of the potential mediators. We also show that the mechanisms underlying the opposing effects of nicotine and CSC on EAE are likely due to distinct effects on microglial viability, activation, and function.
authors.affiliation: Department of Pharmacological Sciences, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America; Program in Neuroscience, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Pharmacological Sciences, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Jillian C
authors.initials: JC
authors.lastname: Nissen
authors.affiliation: Department of Pharmacological Sciences, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Ji
authors.affiliation: Department of Pharmacological Sciences, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America; Program in Neuroscience, School of Medicine, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000171:Acrolein / Q000009:adverse effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009538:Nicotine / Q000627:therapeutic use*; D010455:Peptides; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D010455:Peptides; D012906:Smoke; D009538:Nicotine; D000171:Acrolein