title: Microwave & magnetic (M2) proteomics reveals CNS-specific protein expression waves that precede clinical symptoms of experimental autoimmune encephalomyelitis.
abstract: Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave &magnetic (M(2)) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M(2) proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M(2) proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M(2) proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: Itay
authors.initials: I
authors.lastname: Raphael
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: Swetha
authors.initials: S
authors.lastname: Mahesula
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: Anjali
authors.initials: A
authors.lastname: Purkar
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: David
authors.initials: D
authors.lastname: Black
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: Alexis
authors.initials: A
authors.lastname: Catala
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.
authors.forename: Jonathon A L
authors.initials: JA
authors.lastname: Gelfond
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.affiliation: University of Texas at San Antonio, San Antonio, TX 78249.
authors.forename: William E
authors.initials: WE
authors.lastname: Haskins
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D060328:Magnetic Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D008872:Microwaves; D009103:Multiple Sclerosis / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D013049:Spectrin / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism
chemical_list: D020543:Proteome; D016704:Synapsins; D013049:Spectrin