@article{75ad6a928e924870bccfe18f811feca1,
title = "Distinctive sphingolipid patterns in chronic multiple sclerosis lesions",
abstract = "Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: Active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease. ",
keywords = "Brain lipids, Central nervous system, Ceramide 1-phosphate, Ceramides, Clinical lipidology, Inflammation, Lipidomics, Mass spectrometry, Neurodegeneration, Neurological diseases",
author = "Maria Podbielska and Szulc, {Zdzislaw M.} and Toshio Ariga and Anna Pokryszko-Dragan and Wojciech Fortuna and Ma{\l}gorzata Bilinska and Ryszard Podemski and Ewa Jaskiewicz and Ewa Kurowska and Yu, {Robert K.} and Hogan, {Edward L.}",
note = "Funding Information: Fresh frozen brain tissues were obtained from the Human Brain and Spinal Resource Center, Veterans Affairs West Los Angeles Healthcare Center, 11301 Wilshire Blvd., Los Angeles, CA 90073, which is sponsored by the National Institutes of Health, the National MS Society, and the US Department of Veterans Affairs. Brain tissue specimens were derived from autopsy of patients with clinically diagnosed and neuropathologically confirmed MS (n = 13) and ONDs (n = 15) as well as from three controls who had been diagnosed with diseases without CNS involvement, with essentially normal brain confirmed on autopsy findings, nCNS. OND samples were further subdivided into inflammatory OND (I-OND; n = 5) and noninflammatory OND (NI-OND; n = 10) reference subgroups. Patients{\textquoteright} clinical and autopsy characteristics are provided in Table 1. All procedures performed in this study were in accordance with ethical standards of the institutional ethics committees. Informed consent was obtained at the University of California Los Angeles from the human subjects or their representatives, and Declaration of Helsinki principles were followed. Preservation of anonymity and confidentiality and masking of samples were maintained throughout all studies. Funding Information: This work was supported by National Science Centre (Krakow, Poland) Grant UMO-2013/08/M/NZ3/01040 (to M.P.). Additional partial support was provided by Grants P30 CA138313 and P30 GM103339 from the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC (to Z.M.S.) as well as National Institutes of Health (Bethesda, MD) Grant RO1 NS100839 and US Public Health Service Grant (Washington, DC) RO1 NS100839 (to R.K.Y.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 Podbielska et al.",
year = "2020",
month = nov,
doi = "10.1194/jlr.RA120001022",
language = "English (US)",
volume = "61",
pages = "1464--1479",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "11",
}