Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Spasticity Treatment Ameliorates the Efficacy of Melatonin Therapy in Experimental Autoimmune Encephalomyelitis (EAE) Mouse Model of Multiple Sclerosis

Spasticity Treatment Ameliorates the Efficacy of Melatonin Therapy in Experimental Autoimmune... Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease in the central nervous system (CNS). Melatonin is an effective treatment in MS patients and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Melatonin secretion peaks at 2 AM, concomitant with the time at which the muscles are resting and the body is exerting its antioxidant activity. The current study was designed to investigate combination treatment of baclofen, a muscle relaxant drug, and melatonin in EAE mice. Results showed that melatonin (Mel) alone or in combination with baclofen (Bac + Mel) reduced clinical scores and demyelination by significantly increasing myelin oligodendrocyte glycoprotein (MOG) levels, a marker for mature oligodendrocytes, compared to EAE mice. Moreover, Mel or Bac + Mel therapy caused a significant increase in IL-4 serum levels, an anti-inflammatory cytokine, whereas IFN-γ serum levels, a pro-inflammatory cytokine, were significantly reduced. On the other hand, Mel or Bac + Mel caused a significant reduction in malondialdehyde (MDA) levels, a marker of oxidative stress, in comparison to EAE mice. In contrast, the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) was significantly increased in Mel and Bac + Mel groups. In summary, combination therapy improved clinical scores and tend to enhance the efficiency of melatonin treatment by further promoting remyelination, decreasing inflammation, and stimulating the activity of antioxidant enzymes, which suggests that prior spasticity treatment increases the efficacy of melatonin therapy in EAE mouse model of MS. Further experimental and clinical studies are needed to ensure the beneficial role of this combination strategy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cellular and Molecular Neurobiology Springer Journals

Spasticity Treatment Ameliorates the Efficacy of Melatonin Therapy in Experimental Autoimmune Encephalomyelitis (EAE) Mouse Model of Multiple Sclerosis

Download PDF
7 pages

Loading next page...
 
/lp/springer_journal/spasticity-treatment-ameliorates-the-efficacy-of-melatonin-therapy-in-qCE7EtZE0D
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Neurosciences; Cell Biology; Neurobiology
ISSN
0272-4340
eISSN
1573-6830
DOI
10.1007/s10571-018-0580-y
pmid
29497878
Publisher site
See Article on Publisher Site

Abstract

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease in the central nervous system (CNS). Melatonin is an effective treatment in MS patients and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Melatonin secretion peaks at 2 AM, concomitant with the time at which the muscles are resting and the body is exerting its antioxidant activity. The current study was designed to investigate combination treatment of baclofen, a muscle relaxant drug, and melatonin in EAE mice. Results showed that melatonin (Mel) alone or in combination with baclofen (Bac + Mel) reduced clinical scores and demyelination by significantly increasing myelin oligodendrocyte glycoprotein (MOG) levels, a marker for mature oligodendrocytes, compared to EAE mice. Moreover, Mel or Bac + Mel therapy caused a significant increase in IL-4 serum levels, an anti-inflammatory cytokine, whereas IFN-γ serum levels, a pro-inflammatory cytokine, were significantly reduced. On the other hand, Mel or Bac + Mel caused a significant reduction in malondialdehyde (MDA) levels, a marker of oxidative stress, in comparison to EAE mice. In contrast, the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) was significantly increased in Mel and Bac + Mel groups. In summary, combination therapy improved clinical scores and tend to enhance the efficiency of melatonin treatment by further promoting remyelination, decreasing inflammation, and stimulating the activity of antioxidant enzymes, which suggests that prior spasticity treatment increases the efficacy of melatonin therapy in EAE mouse model of MS. Further experimental and clinical studies are needed to ensure the beneficial role of this combination strategy.

Journal

Cellular and Molecular Neurobiology – Springer Journals

Published: Mar 1, 2018

References

  • Melatonin acts as antioxidant and improves sleep in MS patients
    Adamczyk-Sowa, M; Pierzchala, K; Sowa, P; Mucha, S; Sadowska-Bartosz, I; Adamczyk, J; Hartel, M
  • Continuous intrathecal baclofen infusion for spasticity of cerebral origin
    Albright, AL; Barron, WB; Fasick, MP; Polinko, P; Janosky, J
  • Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance
    Alvarez-Sanchez, N; Cruz-Chamorro, I; Lopez-Gonzalez, A; Utrilla, JC; Fernandez-Santos, JM; Martinez-Lopez, A; Lardone, PJ; Guerrero, JM; Carrillo-Vico, A
  • Pathophysiology of spasticity
    Brown, P
  • melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis
    Chen, SJ; Huang, SH; Chen, JW; Wang, KC; Yang, YR; Liu, PF; Lin, GJ; Sytwu, HK
  • Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches
    Constant, SL; Bottomly, K
  • Evidence for possible role of melatonin in reducing oxidative stress in multiple sclerosis through its effect on SIRT1 and antioxidant enzymes
    Emamgholipour, S; Hossein-Nezhad, A; Sahraian, MA; Askarisadr, F; Ansari, M
  • Melatonin contributes to the seasonality of multiple sclerosis relapses
    Farez, MF; Mascanfroni, ID; Mendez-Huergo, SP; Yeste, A; Murugaiyan, G; Garo, LP; Balbuena Aguirre, ME; Patel, B; Ysrraelit, MC; Zhu, C; Kuchroo, VK; Rabinovich, GA; Quintana, FJ; Correale, J
  • The management of spasticity in multiple sclerosis
    Gelber, DA; Jozefczyk, PB
  • Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: a potential biomarker of multiple sclerosis progression
    Ghareghani, M; Dokoohaki, S; Ghanbari, A; Farhadi, N; Zibara, K; Khodadoust, S; Parishani, M; Ghavamizadeh, M; Sadeghi, H
  • Melatonin increases oligodendrocyte differentiation in cultured neural stem cells
    Ghareghani, M; Sadeghi, H; Zibara, K; Danaei, N; Azari, H; Ghanbari, A
  • Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis
    Ghareghani, M; Zibara, K; Sadeghi, H; Dokoohaki, S; Sadeghi, H; Aryanpour, R; Ghanbari, A
  • Multiple sclerosis—remyelination failure as a cause of disease progression
    Hagemeier, K; Bruck, W; Kuhlmann, T
  • Evaluation of the effects of Sativex (THC BDS: CBD BDS) on inhibition of spasticity in a chronic relapsing experimental allergic autoimmune encephalomyelitis: a model of multiple sclerosis
    Hilliard, A; Stott, C; Wright, S; Guy, G; Pryce, G; Al-Izki, S; Bolton, C; Giovannoni, G
  • Antioxidant effect of muscle relaxants (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by reactive oxygen species
    Jeong, JS; Suh, JK; Cho, ES; Kim, DW; Jeong, MA
  • Melatonin ameliorates autoimmune encephalomyelitis through suppression of intercellular adhesion molecule-1
    Kang, JC; Ahn, M; Kim, YS; Moon, C; Lee, Y; Wie, MB; Lee, YJ; Shin, T
  • Effects of atorvastatin on the Th1/Th2 polarization of ongoing experimental autoimmune myocarditis in Lewis rats
    Liu, W; Li, W-M; Gao, C; Sun, N-L
  • Cannabinoids in the management of spasticity associated with multiple sclerosis
    Malfitano, AM; Proto, MC; Bifulco, M
  • Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis
    Melamud, L; Golan, D; Luboshitzky, R; Lavi, I; Miller, A
  • Effect of intrathecal baclofen delivered by an implanted programmable pump on health related quality of life in patients with severe spasticity
    Middel, B; Kuipers-Upmeijer, H; Bouma, J; Staal, M; Oenema, D; Postma, T; Terpstra, S; Stewart, R
  • Antioxidant therapy in multiple sclerosis
    Mirshafiey, A; Mohsenzadegan, M
  • One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates autoimmune demyelinating disease
    Nashold, FE; Nelson, CD; Brown, LM; Hayes, CE
  • Melatonin promotes oligodendroglial maturation of injured white matter in neonatal rats
    Olivier, P; Fontaine, RH; Loron, G; Steenwinckel, J; Biran, V; Massonneau, V; Kaindl, A; Dalous, J; Charriaut-Marlangue, C; Aigrot, MS; Pansiot, J; Verney, C; Gressens, P; Baud, O
  • Intrathecal baclofen for severe spinal spasticity
    Penn, RD; Savoy, SM; Corcos, D; Latash, M; Gottlieb, G; Parke, B; Kroin, JS
  • Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production
    Powers, SK; Jackson, MJ
  • The melatonin rhythm: both a clock and a calendar
    Reiter, RJ
  • A review of the evidence supporting melatonin’s role as an antioxidant
    Reiter, RJ; Melchiorri, D; Sewerynek, E; Poeggeler, B; Barlow-Walden, L; Chuang, J; Ortiz, GG; Acuna-Castroviejo, D
  • Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis
    Sandyk, R
  • Elevated hydrogen peroxide and decreased catalase and glutathione peroxidase protection are associated with aging sarcopenia
    Sullivan-Gunn, MJ; Lewandowski, PA
  • Multiple sclerosis: current pathophysiological concepts
    Wingerchuk, DM; Lucchinetti, CF; Noseworthy, JH