Advertisement

Combined progressive functional exercise effect on contactin-1 and contactin-2 level in mildly disabled persons with multiple sclerosis

Published:August 08, 2022DOI:https://doi.org/10.1016/j.msard.2022.104095

      Highlights

      • The study provides new insights into the effects of exercise on serum contactin-1 and contactin-2 levels as surrogate markers in axonal function.
      • The role of contactin 1 and contactin 2 is of great importance in monitoring axonal damage in neurodegenerative diseases such as MS and in the beneficial effects of exercise on myelin regeneration and axonal damage.
      • It can be said that exercise may have a neuroprotective effect on neurodegenerative diseases such as MS by increasing contactin-1 and contactin-2 levels.
      • Exercise can be added to new approaches aimed at increasing neural regeneration in PwMS by inducing contactin 1 and contactin 2.

      Abstract

      Background

      Although contactin-1 and contactin-2 are known as two proteins involved in axonal regeneration, it is unclear whether these proteins are induced by exercise in persons with multiple sclerosis (PwMS).

      Objective

      The aim of this study was to determine the serum levels of contactin-1 and contactin-2 in PwMS and to investigate the change of these markers with exercise.

      Methods

      A total of 60 participants with relapsing-remitting MS were divided into groups by stratified randomization. The progressive functional exercise was applied to the intervention group. Participants in the control group continued the treatments and lives of the routines. Participants' contactin-1 and contactin-2, cognitive performance and aerobic capacities were evaluated.

      Results

      The comparison of the pre-and post-study values of contactin-1 and contactin-2 showed significant differences only in the intervention group. The contactin-1 and contactin-2 values were similar between the groups before the exercise, whereas a significant difference was found in favor of the intervention group after the exercise. Paced Auditory Serial Addition Test-3 value increased significantly only in the intervention group.

      Conclusion

      With this study, it was shown for the first time that contactin-1 and contactin-2, which play an important role in axonal regeneration and axonal organization, can be increased by exercise.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Banitalebi E.
        • Ghahfarrokhi M.M.
        • Negaresh R.
        • et al.
        Exercise improves neurotrophins in multiple sclerosis independent of disability status.
        Mult. Scler. Relat. Disord. 2020; 43102143https://doi.org/10.1016/j.msard.2020.102143
        • Bjartmar C.
        • Wujek J.R.
        • Trapp B.D.
        Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease.
        J. Neurol. Sci. 2003; 206: 165-171https://doi.org/10.1016/s0022-510x(02)00069-2
        • Boyle M.E.
        • Berglund E.O.
        • Murai K.K.
        • Weber L.
        • Peles E.
        • Ranscht B.
        Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve.
        Neuron. 2001; 30: 385-397https://doi.org/10.1016/s0896-6273(01)00296-3
        • Chatterjee M.
        • Del Campo M.
        • Morrema T.H.J.
        • et al.
        Contactin-2, a synaptic and axonal protein, is reduced in cerebrospinal fluid and brain tissue in Alzheimer's disease.
        Alzheimers Res. Ther. 2018; 10 (Published 2018 Jun 1): 52https://doi.org/10.1186/s13195-018-0383-x
        • Chatterjee M.
        • Koel-Simmelink M.J.
        • Verberk I.M.
        • et al.
        Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis.
        Mult. Scler. J. Exp. Transl. Clin. 2018; 4 (2055217318819535. Published 2018 Dec 24)https://doi.org/10.1177/2055217318819535
        • Cohen J.
        Stafisfical power analysis for the behavioural sciences.
        Hillside. 2nd ed. Erlbaum, NJ1988: 283
        • Çolakoğlu G.
        • Bergstrom-Tyrberg U.
        • Berglund E.O.
        • Ranscht B.
        Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.
        Proc. Natl. Acad. Sci. U. S. A. 2014; 111: E394-E403https://doi.org/10.1073/pnas.1313769110
        • Dalgas U.
        • Ingemann-Hansen T.
        • Stenager E.
        Physical exercise and MS recommendations.
        Int. MS J. 2009; 16: 5-11
        • Dalgas U.
        • Langeskov-Christensen M.
        • Stenager E.
        • Riemenschneider M.
        • Hvid L.G.
        Exercise as medicine in multiple sclerosis-time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives.
        Curr. Neurol. Neurosci. Rep. 2019; 19 (Published 2019 Nov 13): 88https://doi.org/10.1007/s11910-019-1002-3
        • Derfuss T.
        • Parikh K.
        • Velhin S.
        • et al.
        Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals.
        Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 8302-8307https://doi.org/10.1073/pnas.0901496106
        • Ferguson B.
        • Matyszak M.K.
        • Esiri M.M.
        • Perry V.H.
        Axonal damage in acute multiple sclerosis lesions.
        Brain. 1997; 120: 393-399https://doi.org/10.1093/brain/120.3.393
        • Jalkh G.
        • Abi Nahed R.
        • Macaron G.
        • Rensel M
        Safety of newer disease modifying therapies in multiple sclerosis.
        Vaccines. 2020; 9 (Basel)Published 2020 Dec 26: 12https://doi.org/10.3390/vaccines9010012
        • Kalafatakis I.
        • Savvaki M.
        • Velona T.
        • Karagogeos D.
        Implication of contactins in demyelinating pathologies.
        Life. 2021; 11 (Basel)Published 2021 Jan 13: 51https://doi.org/10.3390/life11010051
        • Klaren R.E.
        • Hubbard E.A.
        • Motl R.W.
        • Pilutti L.A.
        • Wetter N.C.
        • Sutton B.P.
        Objectively measured physical activity is associated with brain volumetric measurements in multiple sclerosis.
        Behav. Neurol. 2015; 2015482536https://doi.org/10.1155/2015/482536
        • Lin J.F.
        • Pan H.C.
        • Ma L.P.
        • Shen Y.Q.
        • Schachner M.
        The cell neural adhesion molecule contactin-2 (TAG-1) is beneficial for functional recovery after spinal cord injury in adult zebrafish.
        PLoS One. 2012; 7: e52376https://doi.org/10.1371/journal.pone.0052376
        • Ma Q.H.
        • Futagawa T.
        • Yang W.L.
        • et al.
        A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.
        Nat. Cell Biol. 2008; 10 ([published correction appears in Nat Cell Biol. 2008 Apr;10(4):497]): 283-294https://doi.org/10.1038/ncb1690
        • Manso C.
        • Querol L.
        • Mekaouche M.
        • Illa I.
        • Devaux J.J.
        Contactin-1 IgG4 antibodies cause paranode dismantling and conduction defects.
        Brain. 2016; 139: 1700-1712https://doi.org/10.1093/brain/aww062
        • Mathieu P.A.
        • Almeira Gubiani M.F.
        • Rodríguez D.
        • Gómez Pinto L.I.
        • Calcagno M.L.
        • Adamo A.M
        Demyelination-remyelination in the central nervous system: ligand-dependent participation of the notch signaling pathway.
        Toxicol. Sci. 2019; ([published online ahead of print, 2019 Jun 6]): kfz130https://doi.org/10.1093/toxsci/kfz130
        • Motl R.W.
        • Fernhall B.
        Accurate prediction of cardiorespiratory fitness using cycle ergometry in minimally disabled persons with relapsing-remitting multiple sclerosis.
        Arch. Phys. Med. Rehabil. 2012; 93: 490-495https://doi.org/10.1016/j.apmr.2011.08.025
        • Motl R.W.
        • Sandroff B.M.
        Exercise as a countermeasure to declining central nervous system function in multiple sclerosis.
        Clin. Ther. 2018; 40: 16-25https://doi.org/10.1016/j.clinthera.2017.12.001
        • Nakahara J.
        • Kanekura K.
        • Nawa M.
        • Aiso S.
        • Suzuki N.
        Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis.
        J. Clin. Investig. 2009; 119: 169-181https://doi.org/10.1172/JCI35440
        • Negaresh R.
        • Motl R.W.
        • Zimmer P.
        • Mokhtarzade M.
        • Baker J.S.
        Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: a systematic review of intervention studies.
        Eur. J. Neurol. 2019; 26: 711-721https://doi.org/10.1111/ene.13929
        • Ocklenburg S.
        • Gerding W.M.
        • Arning L.
        • et al.
        Myelin genes and the corpus callosum: proteolipid protein 1 (PLP1) and contactin 1 (CNTN1) gene variation modulates interhemispheric integration.
        Mol. Neurobiol. 2017; 54: 7908-7916https://doi.org/10.1007/s12035-016-0285-5
        • Oreja-Guevara C.
        • Ayuso Blanco T.
        • Brieva Ruiz L.
        • Hernández Pérez M.Á.
        • Meca-Lallana V.
        • Ramió-Torrentà L
        Cognitive dysfunctions and assessments in multiple sclerosis.
        Front. Neurol. 2019; 10 (Published 2019 Jun 4): 581https://doi.org/10.3389/fneur.2019.00581
        • Riccitelli G.C.
        • Pagani E.
        • Rodegher M.
        • et al.
        Imaging patterns of gray and white matter abnormalities associated with PASAT and SDMT performance in relapsing-remitting multiple sclerosis.
        Mult. Scler. 2019; 25: 204-216https://doi.org/10.1177/1352458517743091
        • Sandroff B.M.
        • Motl R.W.
        • Deluca J.
        The influence of cognitive impairment on the fitness-cognition relationship in multiple sclerosis.
        Med. Sci. Sports Exerc. 2017; 49: 1184-1189https://doi.org/10.1249/MSS.0000000000001215
        • Schutzer S.E.
        • Angel T.E.
        • Liu T.
        • et al.
        Gray matter is targeted in first-attack multiple sclerosis.
        PLoS One. 2013; 8 (Published 2013 Sep 10): e66117https://doi.org/10.1371/journal.pone.0066117
        • Shimoda Y.
        • Watanabe K.
        Contactins: emerging key roles in the development and function of the nervous system.
        Cell Adhes. Migr. 2009; 3: 64-70https://doi.org/10.4161/cam.3.1.7764
        • Teunissen C.E.
        • Iacobaeus E.
        • Khademi M.
        • et al.
        Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis.
        Neurology. 2009; 72: 1322-1329https://doi.org/10.1212/WNL.0b013e3181a0fe3f
        • Thompson A.J.
        • Baranzini S.E.
        • Geurts J.
        • Hemmer B.
        • Ciccarelli O.
        Multiple sclerosis.
        Lancet. 2018; 391: 1622-1636https://doi.org/10.1016/S0140-6736(18)30481-1
        • Traka M.
        • Dupree J.L.
        • Popko B.
        • Karagogeos D.
        The neuronal adhesion protein TAG-1 is expressed by schwann cells and oligodendrocytes and is localized to the juxtaparanodal region of myelinated fibers.
        J. Neurosci. 2002; 22: 3016-3024https://doi.org/10.1523/JNEUROSCI.22-08-03016.2002
        • Trapp B.D.
        • Ransohoff R.
        • Rudick R.
        Axonal pathology in multiple sclerosis: relationship to neurologic disability.
        Curr. Opin. Neurol. 1999; 12: 295-302https://doi.org/10.1097/00019052-199906000-00008
        • van Lierop Z.Y.
        • Wieske L.
        • Koel-Simmelink M.J.
        • et al.
        Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.
        Mult. Scler. 2022; 28: 102-110https://doi.org/10.1177/13524585211010097
        • Wolman M.A.
        • Sittaramane V.K.
        • Essner J.J.
        • Yost H.J.
        • Chandrasekhar A.
        • Halloran M.C.
        Transient axonal glycoprotein-1 (TAG-1) and laminin-alpha1 regulate dynamic growth cone behaviors and initial axon direction in vivo.
        Neural Dev. 2008; 3 (Published 2008 Feb 20): 6https://doi.org/10.1186/1749-8104-3-6
        • Zimmer P.
        • Bloch W.
        • Schenk A.
        • et al.
        High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: a randomized controlled trial.
        Mult. Scler. 2018; 24: 1635-1644https://doi.org/10.1177/1352458517728342