Minocycline effects on the CSF proteome of Experimental Autoimmune Encephalomyelitis rats.
2012 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907Article in journal (Refereed) Published
To identify response biomarkers for pharmaceutical treatment of Multiple Sclerosis, we induced Experimental Autoimmune Encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected fourteen days after EAE induction at the peak of neurological symptoms and proteomics analysis was performed using nano-LC-Orbitrap mass spectrometry. Additionally, the minocycline concentration in CSF was determined using quantitative MALDI-triple-quadrupole tandem mass spectrometry (MALDI-MS/MS) in the selected reaction monitoring (SRM) mode. Fifty percent of the minocycline-treated EAE animals did not show neurological symptoms on day 14 ("responders"), whilst the other half displayed neurological symptoms ("non-responders"), indicating that minocycline delayed disease onset and attenuated disease severity in some, but not all, animals. Neither CSF nor plasma minocycline concentrations correlated with the onset of symptoms or disease severity. Analysis of the proteomics data resulted in a list of 20 differentially abundant proteins between the untreated animals and the responder group of animals. Two of these proteins, complement C3 and carboxypeptidase B2, were validated by quantitative LC-MS/MS in the SRM mode. Differences in the CSF proteome between untreated EAE animals and minocycline-treated responders were similar to the differences between minocycline-treated responders and non-responders (70% overlap). Six proteins that remained unchanged in the minocycline-treated animals but were elevated in untreated EAE animals may be related to the mechanism of action of minocycline.
Place, publisher, year, edition, pages
Minocycline, Biomarker, Proteome, EAE, Mass Spectrometry
Research subject Analytical Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-177368DOI: PMID: 22768796 [PubMed - as supplied by publisher]OAI: oai:DiVA.org:uu-177368DiVA: diva2:540789