{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:32:17Z","timestamp":1782729137232,"version":"3.54.5"},"reference-count":173,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rotary Club of Narellan","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(\u00b1PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(\u00b1PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(\u00b1PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(\u00b1PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the \u2018inside-out\u2019 theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ\u00b1PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the \u2018inside-out\u2019 role of the adaptive immune system in this model over long time periods. Notably, CPZ(\u00b1PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure\/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.<\/jats:p>","DOI":"10.3390\/cells8111314","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"1314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-9196","authenticated-orcid":false,"given":"Monokesh K.","family":"Sen","sequence":"first","affiliation":[{"name":"School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S. M.","family":"Almuslehi","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"},{"name":"Department of Physiology, College of Veterinary Medicine, Diyala University, Diyala, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Gyengesi","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Myers","sequence":"additional","affiliation":[{"name":"School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Shortland","sequence":"additional","affiliation":[{"name":"School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-9638","authenticated-orcid":false,"given":"David A.","family":"Mahns","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-7370","authenticated-orcid":false,"given":"Jens R.","family":"Coorssen","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Faculty of Applied Health Sciences, and Department of Biological Sciences, Faculty of Mathematics and Science, Brock University, St. Catharines, Ontario, ON L2S 3A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/prca.201400141","article-title":"Proteomics of a conundrum: Thoughts on addressing the aetiology versus progression of multiple sclerosis","volume":"9","author":"Partridge","year":"2015","journal-title":"Proteom. Clin. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neubiorev.2019.08.008","article-title":"Behavioural phenotypes in the cuprizone model of central nervous system demyelination","volume":"107","author":"Sen","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12703\/P5-20","article-title":"Pathoetiology of multiple sclerosis: are we barking up the wrong tree?","volume":"5","author":"Stys","year":"2013","journal-title":"F1000Prime Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrn3275","article-title":"Will the real multiple sclerosis please stand up?","volume":"13","author":"Stys","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","article-title":"Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)","volume":"164","author":"Constantinescu","year":"2011","journal-title":"Br. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/brain\/awl075","article-title":"Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research","volume":"129","author":"Gold","year":"2006","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Glatigny, S., and Bettelli, E. (2018). Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS). Cold Spring Harb. Perspect. Med., 8.","DOI":"10.1101\/cshperspect.a028977"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bittner, S., Afzali, A.M., Wiendl, H., and Meuth, S.G. (2014). Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL\/6 mice. J. Vis. Exp.","DOI":"10.3791\/51275"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10647","DOI":"10.3390\/ijms130810647","article-title":"Molecular mechanisms of oligodendrocyte injury in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"13","author":"Patel","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/1742-2094-9-233","article-title":"Pain in experimental autoimmune encephalitis: a comparative study between different mouse models","volume":"9","author":"Lu","year":"2012","journal-title":"J. Neuroinflammation."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.4049\/jimmunol.1401108","article-title":"Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination","volume":"195","author":"Evonuk","year":"2015","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.molmed.2010.11.006","article-title":"EAE: imperfect but useful models of multiple sclerosis","volume":"17","author":"Hart","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.neuro.30.051606.094313","article-title":"Multiple sclerosis: an immune or neurodegenerative disorder?","volume":"31","author":"Trapp","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00401-016-1631-4","article-title":"Multiple sclerosis: experimental models and reality","volume":"133","author":"Lassmann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jneuroim.2016.08.013","article-title":"Contribution of EAE to understanding and treating multiple sclerosis","volume":"304","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/eji.200939568","article-title":"EAE: an immunologist\u2019s magic eye","volume":"39","author":"Krishnamoorthy","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/ana.20743","article-title":"Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis","volume":"58","author":"Sriram","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.msard.2014.06.003","article-title":"EAE is not a useful model for demyelinating disease","volume":"3","author":"Behan","year":"2014","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1074-7613(01)00143-1","article-title":"Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis","volume":"14","author":"Flugel","year":"2001","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1016\/j.febslet.2011.08.004","article-title":"The molecular basis of neurodegeneration in multiple sclerosis","volume":"585","author":"Lassmann","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1093\/brain\/awh578","article-title":"Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?","volume":"128","author":"Friese","year":"2005","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/ana.410190610","article-title":"Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions","volume":"19","author":"Hauser","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1084\/jem.192.3.393","article-title":"Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction","volume":"192","author":"Babbe","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/nn.3168","article-title":"Animal models of multiple sclerosis: the good, the bad and the bottom line","volume":"15","author":"Ransohoff","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/jnnp.2008.148767","article-title":"Regional variations in the extent and pattern of grey matter demyelination in multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex, deep grey matter nuclei and the spinal cord","volume":"80","author":"Gilmore","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lavi, E., and Constantinescu, C.S. (2005). Histopathology of EAE. Experimental Models of Multiple Sclerosis, Springer US.","DOI":"10.1007\/b135502"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0165-5728(00)00309-X","article-title":"Characterization of acute versus chronic relapsing autoimmune encephalomyelitis in DA rats","volume":"108","author":"Tanuma","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_28","first-page":"630","article-title":"Analysis of the mitochondrial proteome in multiple sclerosis cortex","volume":"1812","author":"Broadwater","year":"2011","journal-title":"BBA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cca.2011.02.004","article-title":"The experimental autoimmune encephalomyelitis model for proteomic biomarker studies: from rat to human","volume":"412","author":"Rosenling","year":"2011","journal-title":"Clin. Chim. Acta."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1136\/jim-2016-000339","article-title":"Update on disease-modifying therapies for multiple sclerosis","volume":"65","author":"Vargas","year":"2017","journal-title":"J. Investig. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1073\/pnas.1721115115","article-title":"Biochemically altered myelin triggers autoimmune demyelination","volume":"115","author":"Caprariello","year":"2018","journal-title":"PNAS"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ana.20016","article-title":"Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion","volume":"55","author":"Barnett","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/ana.21800","article-title":"Multiple sclerosis: distribution of inflammatory cells in newly forming lesions","volume":"66","author":"Henderson","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q","article-title":"Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination","volume":"47","author":"Lucchinetti","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1750-3639.1996.tb00854.x","article-title":"Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis","volume":"6","author":"Lucchinetti","year":"1996","journal-title":"Brain Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/01913129409016267","article-title":"Ultrastructure of multiple sclerosis","volume":"18","author":"Rodriguez","year":"1994","journal-title":"Ultrastruct. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nn.4193","article-title":"Oligodendrocyte death results in immune-mediated CNS demyelination","volume":"19","author":"Traka","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0024-3205(67)90356-6","article-title":"Studies on the induction of hydrocephalus and spongy degeneration by cuprizone feeding and attempts to antidote the toxicity","volume":"6","author":"Carlton","year":"1967","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1750-3639.2001.tb00385.x","article-title":"The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system","volume":"11","author":"Matsushima","year":"2001","journal-title":"Brain Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0022-510X(87)90268-1","article-title":"Decrease in oligodendrocyte carbonic anhydrase activity preceding myelin degeneration in cuprizone induced demyelination","volume":"79","author":"Komoly","year":"1987","journal-title":"J. Neurol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1007\/s00018-005-5073-8","article-title":"Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment","volume":"62","author":"Zatta","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2015.02.009","article-title":"Altered transition metal homeostasis in the cuprizone model of demyelination","volume":"48","author":"Moldovan","year":"2015","journal-title":"Neurotoxicol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s10571-018-0578-5","article-title":"Cuprizone Administration Alters the Iron Metabolism in the Mouse Model of Multiple Sclerosis","volume":"38","author":"Varga","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/j.1471-4159.1973.tb07569.x","article-title":"Enzymic activities and sodium, potassium and copper concentrations in mouse brain and liver after cuprizone treatment in vivo","volume":"21","author":"Venturini","year":"1973","journal-title":"J. Neurochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2008.05570.x","article-title":"The life, death, and replacement of oligodendrocytes in the adult CNS","volume":"107","author":"McTigue","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0733-8619(18)30060-4","article-title":"Oligodendrocytes and myelin","volume":"13","author":"McLaurin","year":"1995","journal-title":"Neurol. Clin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0166-2236(00)01742-2","article-title":"Demyelinating diseases: from pathogenesis to repair strategies","volume":"24","author":"Liblau","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12031-017-0888-y","article-title":"The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model","volume":"61","author":"Tejedor","year":"2017","journal-title":"J. Mol. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12154-015-0138-0","article-title":"An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis","volume":"9","author":"Partridge","year":"2016","journal-title":"J. Chem. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e0129217","DOI":"10.1371\/journal.pone.0129217","article-title":"Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis","volume":"10","author":"Solti","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1021\/pr050054d","article-title":"Postfractionation for enhanced proteomic analyses: routine electrophoretic methods increase the resolution of standard 2D-PAGE","volume":"4","author":"Butt","year":"2005","journal-title":"J. Proteome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/pmic.201300424","article-title":"Top-down proteomics: enhancing 2D gel electrophoresis from tissue processing to high-sensitivity protein detection","volume":"14","author":"Wright","year":"2014","journal-title":"Proteomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jprot.2018.02.002","article-title":"Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth","volume":"178","author":"Hyett","year":"2018","journal-title":"J. Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jprot.2014.03.035","article-title":"2DE: the phoenix of proteomics","volume":"104","author":"Oliveira","year":"2014","journal-title":"J. Proteom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"440","DOI":"10.3390\/proteomes3040440","article-title":"Proteomics Is Analytical Chemistry: Fitness-for-Purpose in the Application of Top-Down and Bottom-Up Analyses","volume":"3","author":"Coorssen","year":"2015","journal-title":"Proteomes"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kurgan, N., Noaman, N., Pergande, M.R., Cologna, S.M., Coorssen, J.R., and Klentrou, P. (2019). Changes to the Human Serum Proteome in Response to High Intensity Interval Exercise: A Sequential Top-Down Proteomic Analysis. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00362"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00401-009-0591-3","article-title":"The cuprizone animal model: new insights into an old story","volume":"118","author":"Kipp","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fncel.2014.00073","article-title":"Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned","volume":"8","author":"Gudi","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0165-5728(98)00168-4","article-title":"Microglial\/macrophage accumulation during cuprizone-induced demyelination in C57BL\/6 mice","volume":"92","author":"Hiremath","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jneuroim.2015.10.012","article-title":"Pertussis toxin promotes relapsing-remitting experimental autoimmune encephalomyelitis in Lewis rats","volume":"289","author":"Mohajeri","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4049\/jimmunol.169.1.117","article-title":"Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund\u2019s adjuvant: induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells","volume":"169","author":"Hofstetter","year":"2002","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Gao, Z., Nissen, J.C., Ji, K., and Tsirka, S.E. (2014). The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107979"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jneuroim.2010.08.011","article-title":"Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE","volume":"229","author":"Bennett","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_64","unstructured":"Almuslehi, M.S.M., Sen, M.K., Mahns, D.A., Shortland, P.J., and Coorssen, J.R. (2018, January 3\u20136). Blood Brain Barrier Disruption Facilitates CD8 T Cells infiltration into the CNS of Orchiectomized Cuprizone Treated Mice. Proceedings of the Australasian Neuroscience Society, Brisbane Convention & Exhibition Centre, Brisbane, Australia."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11095-017-2326-9","article-title":"Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice","volume":"35","author":"Gyengesi","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00429-013-0516-8","article-title":"Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods","volume":"219","author":"Gyengesi","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jneumeth.2005.10.014","article-title":"A modified technique for high-resolution staining of myelin","volume":"153","author":"Pistorio","year":"2006","journal-title":"J. Neurosci. Methods."},{"key":"ref_68","unstructured":"Paxinos, G., and Franklin, K. (2012). Paxinos and Franklin\u2019s the Mouse Brain in Stereotaxic Coordinates, Academic Press. [Fourth ed.]."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1750-3639.2008.00230.x","article-title":"SJL mice exposed to cuprizone intoxication reveal strain and gender pattern differences in demyelination","volume":"19","author":"Taylor","year":"2009","journal-title":"Brain Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.bbi.2017.05.015","article-title":"The role of IL-6 in neurodevelopment after prenatal stress","volume":"65","author":"Gumusoglu","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1021\/pr0503634","article-title":"Pre-extraction sample handling by automated frozen disruption significantly improves subsequent proteomic analyses","volume":"5","author":"Butt","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1074\/mcp.M700083-MCP200","article-title":"Enabling coupled quantitative genomics and proteomics analyses from rat spinal cord samples","volume":"6","author":"Butt","year":"2007","journal-title":"Mol. Cell. Proteom."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wright, E.P., Prasad, K.A., Padula, M.P., and Coorssen, J.R. (2014). Deep imaging: how much of the proteome does current top-down technology already resolve?. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086058"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jprot.2013.01.027","article-title":"Coomassie blue staining for high sensitivity gel-based proteomics","volume":"90","author":"Gauci","year":"2013","journal-title":"J. Proteom."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ab.2018.05.012","article-title":"Coomassie does it (better): A Robin Hood approach to total protein quantification","volume":"556","author":"Noaman","year":"2018","journal-title":"Anal. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.1074\/mcp.M112.021881","article-title":"Coomassie blue as a near-infrared fluorescent stain: a systematic comparison with Sypro Ruby for in-gel protein detection","volume":"12","author":"Butt","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1021\/pr0700246","article-title":"Assessing detection methods for gel-based proteomic analyses","volume":"6","author":"Harris","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1002\/elps.201700190","article-title":"Coomassie staining provides routine (sub)femtomole in-gel detection of intact proteoforms: Expanding opportunities for genuine Top-down Proteomics","volume":"38","author":"Noaman","year":"2017","journal-title":"Electrophoresis"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"D\u2019Silva, A.M., Hyett, J.A., and Coorssen, J.R. (2017). A Routine \u2018Top-Down\u2019 Approach to Analysis of the Human Serum Proteome. Proteomes, 5.","DOI":"10.3390\/proteomes5020013"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12154-014-0125-x","article-title":"Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1","volume":"8","author":"Stimpson","year":"2015","journal-title":"J. Chem. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpara.2016.11.004","article-title":"Comparative proteomic analysis of two pathogenic Tritrichomonas foetus genotypes: there is more to the proteome than meets the eye","volume":"47","author":"Stroud","year":"2017","journal-title":"Int. J. Parasitol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1093\/nar\/gky092","article-title":"UniProt: the universal protein knowledgebase","volume":"46","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7140","DOI":"10.1038\/srep07140","article-title":"Quantitative proteomic analysis of meningiomas for the identification of surrogate protein markers","volume":"4","author":"Sharma","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.3389\/fmicb.2016.01817","article-title":"Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration","volume":"7","author":"Hossain","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"De Las Rivas, J., and Fontanillo, C. (2010). Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLoS Comput. Biol., 6.","DOI":"10.1371\/journal.pcbi.1000807"},{"key":"ref_87","first-page":"131","article-title":"Metabolic response to glatiramer acetate therapy in multiple sclerosis patients","volume":"6","author":"Ferramosca","year":"2016","journal-title":"BBA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1002\/pmic.201200044","article-title":"Proteome analysis of spinal cord during the clinical course of monophasic experimental autoimmune encephalomyelitis","volume":"12","author":"Farias","year":"2012","journal-title":"Proteomics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"M110.000042","DOI":"10.1074\/mcp.M110.000042","article-title":"A novel unbiased proteomic approach to detect the reactivity of cerebrospinal fluid in neurological diseases","volume":"10","author":"Menon","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/pmic.200300732","article-title":"New antigenic candidates in multiple sclerosis: identification by serological proteome analysis","volume":"4","author":"Almeras","year":"2004","journal-title":"Proteomics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/jnc.13142","article-title":"Proteomics-level analysis of myelin formation and regeneration in a mouse model for Vanishing White Matter disease","volume":"134","author":"Geiger","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1021\/pr0504788","article-title":"Lumbar cerebrospinal fluid proteome in multiple sclerosis: characterization by ultrafiltration, liquid chromatography, and mass spectrometry","volume":"5","author":"Noben","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/prca.200800155","article-title":"Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis","volume":"3","author":"Jastorff","year":"2009","journal-title":"Proteom. Clin. Appl."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Linker, R.A., Brechlin, P., Jesse, S., Steinacker, P., Lee, D.H., Asif, A.R., Jahn, O., Tumani, H., Gold, R., and Otto, M. (2009). Proteome profiling in murine models of multiple sclerosis: identification of stage specific markers and culprits for tissue damage. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007624"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/ana.1077","article-title":"Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage","volume":"50","author":"Werner","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jchromb.2004.10.073","article-title":"Extraction and proteomic analysis of proteins from normal and multiple sclerosis postmortem brain","volume":"815","author":"Newcombe","year":"2005","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3389\/fimmu.2018.00490","article-title":"Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice","volume":"9","author":"Martin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1021\/pr070012k","article-title":"Identification of differentially expressed proteins in experimental autoimmune encephalomyelitis (EAE) by proteomic analysis of the spinal cord","volume":"6","author":"Liu","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s12031-010-9354-9","article-title":"Proteomic analysis of demyelinated and remyelinating brain tissue following dietary cuprizone administration","volume":"42","author":"Werner","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jprot.2013.06.008","article-title":"Proteome analysis of post-transplantation recovery mechanisms of an EAE model of multiple sclerosis treated with embryonic stem cell-derived neural precursors","volume":"94","author":"Fazeli","year":"2013","journal-title":"J. Proteom."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1007\/s00415-010-5863-2","article-title":"Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis","volume":"258","author":"Axelsson","year":"2011","journal-title":"J. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1477-5956-7-25","article-title":"Altered proteolytic events in experimental autoimmune encephalomyelitis discovered by iTRAQ shotgun proteomics analysis of spinal cord","volume":"7","author":"Jain","year":"2009","journal-title":"Proteome Sci."},{"key":"ref_103","first-page":"315406","article-title":"Neurofilament proteins as body fluid biomarkers of neurodegeneration in multiple sclerosis","volume":"2011","author":"Gresle","year":"2011","journal-title":"Mult. Scler. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jneuroim.2009.03.002","article-title":"PBMCs protein expression profile in relapsing IFN-treated multiple sclerosis: A pilot study on relation to clinical findings and brain atrophy","volume":"210","author":"Vergara","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1002\/pmic.200900507","article-title":"Proteome analysis of brain in murine experimental autoimmune encephalomyelitis","volume":"10","author":"Fazeli","year":"2010","journal-title":"Proteomics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/2051-5960-1-37","article-title":"Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination","volume":"1","author":"McMahon","year":"2013","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1191\/1352458504ms1089oa","article-title":"The 14-3-3 protein in multiple sclerosis: a marker of disease severity","volume":"10","author":"Colucci","year":"2004","journal-title":"Mult. Scler."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bbr.2017.05.045","article-title":"Increased central dopaminergic activity might be involved in the behavioral abnormality of cuprizone exposure mice","volume":"331","author":"Chang","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.toxlet.2007.01.010","article-title":"Behavioral deficits in the cuprizone-induced murine model of demyelination\/remyelination","volume":"169","author":"Torrente","year":"2007","journal-title":"Toxicol. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.20141656","article-title":"Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0003-2697(02)00015-5","article-title":"Quantitative femto- to attomole immunodetection of regulated secretory vesicle proteins critical to exocytosis","volume":"307","author":"Coorssen","year":"2002","journal-title":"Anal. Biochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.2353\/ajpath.2007.060783","article-title":"Microglial recruitment, activation, and proliferation in response to primary demyelination","volume":"170","author":"Remington","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/j.1462-5822.2006.00813.x","article-title":"Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model","volume":"9","author":"Kugler","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.neubiorev.2014.10.004","article-title":"Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis","volume":"47","author":"Praet","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/01926230600867743","article-title":"Normal structure, function, and histology of the spleen","volume":"34","author":"Cesta","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/01926230600865549","article-title":"Normal structure, function and histology of the thymus","volume":"34","author":"Pearse","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0165-5728(01)00394-0","article-title":"Cuprizone and piperonyl butoxide, proposed inhibitors of T-cell function, attenuate experimental allergic encephalomyelitis in SJL mice","volume":"119","author":"Emerson","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jneuroim.2012.01.010","article-title":"Cuprizone inhibits demyelinating leukomyelitis by reducing immune responses without virus exacerbation in an infectious model of multiple sclerosis","volume":"244","author":"Herder","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jneuroim.2009.02.013","article-title":"Demyelination caused by the copper chelator cuprizone halts T cell mediated autoimmune neuroinflammation","volume":"210","author":"Mana","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev.immunol.21.120601.141110","article-title":"T cell anergy","volume":"21","author":"Schwartz","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.coi.2004.01.013","article-title":"T-cell anergy","volume":"16","author":"Im","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.4049\/jimmunol.172.7.3983","article-title":"IL-2, regulatory T cells, and tolerance","volume":"172","author":"Nelson","year":"2004","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"6794","DOI":"10.1073\/pnas.89.15.6794","article-title":"Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity","volume":"89","author":"Bala","year":"1992","journal-title":"PNAS"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1093\/jn\/129.3.596","article-title":"Transcriptional regulation of interleukin-2 gene expression is impaired by copper deficiency in Jurkat human T lymphocytes","volume":"129","author":"Hopkins","year":"1999","journal-title":"J. Nutr."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.4049\/jimmunol.174.9.5583","article-title":"A pivotal role for the multifunctional calcium\/calmodulin-dependent protein kinase II in T cells: from activation to unresponsiveness","volume":"174","author":"Lin","year":"2005","journal-title":"J. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0092-8674(00)80681-9","article-title":"A role for CaMKII in T cell memory","volume":"100","author":"Bui","year":"2000","journal-title":"Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm.3861","article-title":"Repurposing a leukocyte elastase inhibitor for neuropathic pain","volume":"21","author":"Weyer","year":"2015","journal-title":"Nat. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1089\/ars.2009.2465","article-title":"A role for protein disulfide isomerase in the early folding and assembly of MHC class I molecules","volume":"11","author":"Kang","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mito.2017.10.006","article-title":"Mitochondrial activity in T cells","volume":"41","author":"Mittelbrunn","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2015.11.002","article-title":"Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy","volume":"23","author":"Sukumar","year":"2016","journal-title":"Cell. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/pmic.201300268","article-title":"Ten years of proteomics in multiple sclerosis","volume":"14","author":"Farias","year":"2014","journal-title":"Proteomics."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1074\/mcp.M113.033340","article-title":"Discovery of novel disease-specific and membrane-associated candidate markers in a mouse model of multiple sclerosis","volume":"13","author":"Dagley","year":"2014","journal-title":"Mol. Cell. Proteom."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/prca.200700315","article-title":"Proteomic strategies in multiple sclerosis and its animal models","volume":"1","author":"Elkabes","year":"2007","journal-title":"Proteom. Clin. Appl."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/elps.201700330","article-title":"How many proteins can be identified in a 2DE gel spot within an analysis of a complex human cancer tissue proteome?","volume":"39","author":"Zhan","year":"2018","journal-title":"Electrophoresis"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neuint.2017.08.008","article-title":"1,25-Dihydroxyvitamin-D3 induces brain proteomic changes in cuprizone mice during remyelination involving calcium proteins","volume":"112","author":"Oveland","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1002\/pmic.200700131","article-title":"Methods for the detection and analysis of protein-protein interactions","volume":"7","author":"Berggard","year":"2007","journal-title":"Proteomics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1021\/pr500158r","article-title":"Quantitative proteome profiling of CNS-infiltrating autoreactive CD4+ cells reveals selective changes during experimental autoimmune encephalomyelitis","volume":"13","author":"Turvey","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.mam.2005.07.001","article-title":"Iron, oxidative stress and human health","volume":"26","author":"Puntarulo","year":"2005","journal-title":"Mol. Asp. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3109\/15376516.2016.1172284","article-title":"Toxicity of cuprizone a Cu(2+) chelating agent on isolated mouse brain mitochondria: a justification for demyelination and subsequent behavioral dysfunction","volume":"26","author":"Faizi","year":"2016","journal-title":"Toxicol. Mech. Methods."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial fission, fusion, and stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science"},{"key":"ref_141","first-page":"266","article-title":"Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination","volume":"65","author":"Acs","year":"2012","journal-title":"Ideggyogy Sz."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1007\/s11064-008-9792-8","article-title":"Activation of inflammatory response by a combination of growth factors in cuprizone-induced demyelinated brain leads to myelin repair","volume":"33","author":"Biancotti","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1523\/JNEUROSCI.3430-11.2012","article-title":"The energetics of CNS white matter","volume":"32","author":"Harris","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00401-009-0601-5","article-title":"Oligodendrocytes: biology and pathology","volume":"119","author":"Bradl","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1177\/1352458514533400","article-title":"Glutathione in multiple sclerosis: more than just an antioxidant?","volume":"20","author":"Carvalho","year":"2014","journal-title":"Mult. Scler."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1177\/153537020623100903","article-title":"Metallothionein redox cycle and function","volume":"231","author":"Kang","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/(SICI)1098-1136(199804)22:4<408::AID-GLIA10>3.0.CO;2-#","article-title":"Distribution of mitochondrial manganese superoxide dismutase among rat glial cells in culture","volume":"22","author":"Pinteaux","year":"1998","journal-title":"Glia"},{"key":"ref_148","first-page":"506","article-title":"Oxidative stress and its impact on neurons and glia in multiple sclerosis lesions","volume":"1862","author":"Lassmann","year":"2016","journal-title":"BBA."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fnins.2015.00264","article-title":"The unfolded protein response in multiple sclerosis","volume":"9","author":"Stone","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/intimm\/dxg022","article-title":"Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains","volume":"15","author":"Cwiklinska","year":"2003","journal-title":"Int. Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.clineuro.2004.02.019","article-title":"Microarray gene expression profiling of chronic active and inactive lesions in multiple sclerosis","volume":"106","author":"Mycko","year":"2004","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"054901","DOI":"10.1063\/1.4927655","article-title":"Dynamics of protein aggregation and oligomer formation governed by secondary nucleation","volume":"143","author":"Michaels","year":"2015","journal-title":"J. Chem. Phys."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1111\/febs.14587","article-title":"Crucial role of protein oligomerization in the pathogenesis of Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"285","author":"Choi","year":"2018","journal-title":"FEBS J."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e00111","DOI":"10.1042\/AN20120088","article-title":"Increased carbonylation, protein aggregation and apoptosis in the spinal cord of mice with experimental autoimmune encephalomyelitis","volume":"5","author":"Dasgupta","year":"2013","journal-title":"ASN Neuro."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"David, M.A., and Tayebi, M. (2014). Detection of Protein Aggregates in Brain and Cerebrospinal Fluid Derived from Multiple Sclerosis Patients. Front. Neurol., 5.","DOI":"10.3389\/fneur.2014.00251"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/emboj.2013.74","article-title":"Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein","volume":"32","author":"Frohlich","year":"2013","journal-title":"EMBO J."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1074\/jbc.M115.680025","article-title":"Dynamin-related Protein 1 Oligomerization in Solution Impairs Functional Interactions with Membrane-anchored Mitochondrial Fission Factor","volume":"291","author":"Clinton","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1046\/j.1432-1033.2003.03808.x","article-title":"Dimerization and oligomerization of the chaperone calreticulin","volume":"270","author":"Jorgensen","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1191\/1352458504ms1023oa","article-title":"Proteomic analysis of multiple sclerosis cerebrospinal fluid","volume":"10","author":"Hammack","year":"2004","journal-title":"Mult. Scler."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1177\/1352458507076406","article-title":"Cerebrospinal fluid proteome profile in multiple sclerosis","volume":"13","author":"Lehmensiek","year":"2007","journal-title":"Mult. Scler."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3389\/fncel.2018.00473","article-title":"The Role of Glial Cells and Synapse Loss in Mouse Models of Alzheimer\u2019s Disease","volume":"12","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/glia.22966","article-title":"Dark microglia: A new phenotype predominantly associated with pathological states","volume":"64","author":"Bisht","year":"2016","journal-title":"Glia"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0014-2999(02)01847-2","article-title":"Excitotoxicity in glial cells","volume":"447","author":"Matute","year":"2002","journal-title":"Eur. J. Pharm."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1289\/ehp.7826135","article-title":"Central neurotransmitter function and its behavioral correlates in man","volume":"26","author":"Hanin","year":"1978","journal-title":"Env. Health Perspect."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/ana.22337","article-title":"Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients","volume":"69","author":"Dutta","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/ana.23860","article-title":"Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors","volume":"73","author":"Dutta","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2045-8118-9-10","article-title":"Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation","volume":"9","author":"Schellenberg","year":"2012","journal-title":"Fluids Barriers CNS"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0165-5728(99)00242-8","article-title":"Analysis of experimental autoimmune encephalomyelitis induced in F344 rats by pertussis toxin administration","volume":"104","author":"Arimoto","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_169","first-page":"653","article-title":"The effects of Bordetella pertussis vaccine on cerebral vascular permeability","volume":"57","author":"Amiel","year":"1976","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0091-3057(96)00234-1","article-title":"Time-dependent effects of in vivo pertussis toxin on morphine analgesia and G-proteins in mice","volume":"56","author":"Shah","year":"1997","journal-title":"Pharm. Biochem. Behav."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1002\/pmic.201000245","article-title":"Achievements and perspectives of top-down proteomics","volume":"10","author":"Armirotti","year":"2010","journal-title":"Proteomics"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jprot.2017.03.002","article-title":"The benefits (and misfortunes) of SDS in top-down proteomics","volume":"175","author":"Kachuk","year":"2018","journal-title":"J. Proteom."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2144\/000113900","article-title":"Tearing the top off \u2019Top-Down\u2019 Proteomics","volume":"53","author":"Perkel","year":"2012","journal-title":"Biotechniques"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/11\/1314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:29:06Z","timestamp":1760189346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/11\/1314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,24]]},"references-count":173,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["cells8111314"],"URL":"https:\/\/doi.org\/10.3390\/cells8111314","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,24]]}}}