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Protective effect and mechanism of nicotinamide adenine dinucleotide against optic neuritis in mice with experimental autoimmune encephalomyelitis.
Guo, Jiangyuan; Li, Bin; Wang, Jueqiong; Guo, Ruoyi; Tian, Ye; Song, Shuang; Guo, Li.
Afiliação
  • Guo J; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Li B; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Wang J; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Guo R; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Tian Y; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Song S; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Guo L; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Electronic address: guoli6@163.com.
Int Immunopharmacol ; 98: 107846, 2021 Sep.
Article em En | MEDLINE | ID: mdl-34174704
Patients with multiple sclerosis (MS) are commonly accompanied by optic neuritis (ON) that causes retinal ganglion cell (RGC) death and even vision loss. Nicotinamide adenine dinucleotide (NAD+) can protect against cell apoptosis and attenuate MS-triggered symptoms. However, the effect of NAD+ on MS-triggered ON remains unclear. Herein, experimental autoimmune encephalomyelitis (EAE) was established by immunizing female C57BL/6 mice with MOG35-55 peptide. To investigate the effect of NAD+ on ON prevention and treatment, EAE mice received 250 mg/kg NAD+ daily via intraperitoneal injection after immunization and EAE onset, respectively. EX-527 (10 mg/kg, SIRT1 inhibitor) was intraperitoneally injected every two days to explore the role of SIRT1 in NAD+-induced therapeutic effect on EAE. NAD+ intervention attenuated the severity of EAE in mice. NAD+ intervention relieved inflammatory infiltration and CD3+ and CD4+ cell infiltration and decreased the number and activation of microglia and astrocytes in the optic nerve. NAD+ intervention also attenuated demyelination, axonal loss, oligodendrocyte apoptosis and oligodendrocyte progenitor cell recruitment and proliferation in the optic nerve and protected against RGC apoptosis in the retina. NAD+ intervention decreased pro-inflammatory cytokine mRNA and pro-apoptotic protein expression and enhanced anti-inflammatory cytokine mRNA expression and the SIRT1 signaling in the optic nerve and retina and regulated the Th1/Th17/Tregs immune response in the spleen. In addition, EX-527 reversed the therapeutic effect of NAD+ on EAE, suggesting that NAD+ prevented MS-triggered ON by activating the SIRT1 signaling pathway. This study shows the potential of NAD+ to be used as a drug in preventing and treating MS-related ON.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Óptico / Retina / Células Ganglionares da Retina / Oligodendroglia / Neurite Óptica / Subpopulações de Linfócitos T / Células Th1 / Glicoproteína Mielina-Oligodendrócito / NAD Limite: Animals / Female / Humans Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Óptico / Retina / Células Ganglionares da Retina / Oligodendroglia / Neurite Óptica / Subpopulações de Linfócitos T / Células Th1 / Glicoproteína Mielina-Oligodendrócito / NAD Limite: Animals / Female / Humans Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China