Profiling and identification of cerebrospinal fluid proteins in a rat EAE model of multiple sclerosis.
The experimental autoimmune encephalomyelitis (EAE) model resembles certain aspects of multiple sclerosis (MScl), with common features such as motor dysfunction, axonal degradation, and infiltration of T-cells. We studied the cerebrospinal fluid (CSF) proteome in the EAE rat model to identify proteomic changes relevant for MScl disease pathology. EAE was induced in male Lewis rats by injection of myelin basic protein (MBP) together with complete Freund's adjuvant (CFA). An inflammatory control group was injected with CFA alone, and a nontreated group served as healthy control. CSF was collected at day 10 and 14 after immunization and analyzed by bottom-up proteomics on Orbitrap LC-MS and QTOF LC-MS platforms in two independent laboratories. By combining results, 44 proteins were discovered to be significantly increased in EAE animals compared to both control groups, 25 of which have not been mentioned in relation to the EAE model before. Lysozyme C1, fetuin B, T-kininogen, serum paraoxonase/arylesterase 1, glutathione peroxidase 3, complement C3, and afamin are among the proteins significantly elevated in this rat EAE model. Two proteins, afamin and complement C3, were validated in an independent sample set using quantitative selected reaction monitoring mass spectrometry. The molecular weights of the identified differentially abundant proteins indicated an increased transport across the blood-brain barrier (BBB) at the peak of the disease, caused by an increase in BBB permeability.
Department of Analytical Biochemistry, Centre for Pharmacy, University of Groningen, Groningen, The Netherlands.
Therese
T
Rosenling
Marcel P
MP
Stoop
Amos
A
Attali
Hans
H
van Aken
Ernst
E
Suidgeest
Christin
C
Christin
Christoph
C
Stingl
Frank
F
Suits
Peter
P
Horvatovich
Rogier Q
RQ
Hintzen
Tinka
T
Tuinstra
Rainer
R
Bischoff
Theo M
TM
Luider
D000818:Animals; D001835:Body Weight; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000134:cerebrospinal fluid*; D008297:Male; D013058:Mass Spectrometry; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D010243:Paralysis / Q000134:cerebrospinal fluid; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew
D002556:Cerebrospinal Fluid Proteins; D020543:Proteome