title: Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice.
abstract: Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial functions, cellular energy metabolism and calcium homeostasis. In this study, we investigated the effect of NAD(+) administration for the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical animal model of multiple sclerosis (MS), was induced by subcutaneous injection of myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg (body weight) NAD(+) in PBS administered intraperitoneally once daily. We observed that NAD(+) treatment could lessen the severity of EAE. Additionally, NAD(+) treatment attenuated pathological injuries of EAE mice. We also found that the AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1(SIRT1) pathway was activated in the NAD(+)-treated mice and NAD(+) treatment suppressed pro-inflammatory T cell responses. Our findings demonstrated that NAD(+) could be an effective and promising agent to treat multiple sclerosis and its effects on other autoimmune diseases should be explored.
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Jueqiong
authors: J
authors: Wang
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Congying
authors: C
authors: Zhao
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Peng
authors: P
authors: Kong
authors: Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Heping West Road 215, Shijiazhuang, Hebei 050000, China.
authors: Huanhuan
authors: H
authors: Sun
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Zhe
authors: Z
authors: Sun
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Guanyun
authors: G
authors: Bian
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China.
authors: Yafei
authors: Y
authors: Sun
authors: Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei 050000, China. Electronic address: guoli6@163.com.
authors: Li
authors: L
authors: Guo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009243:NAD / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects*
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D009243:NAD; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: AMPK/SIRT1; Experimental autoimmune encephalomyelitis; Immunomodulatory effect; Multiple sclerosis; NAD(+)