Cuprizone‐induced demyelination and demyelination‐associated inflammation result in different proton magnetic resonance metabolite spectra. (April 2015)

• Record Type: Journal Article
• Authors: Praet, Jelle; Orije, Jasmien; Kara, Firat; Guglielmetti, Caroline; Santermans, Eva; Daans, Jasmijn; Hens, Niel; Verhoye, Marleen; Berneman, Zwi; Ponsaerts, Peter; Van der Linden, Annemie
• Is Part Of: NMR in biomedicine. Volume 28:Number 4(2015:Apr.)
• Page Start: 505
• Page End: 513
• Publication Date: 2015-04
• Subjects: CX3CR1 -- cuprizone -- demyelination -- spectroscopy -- MRI; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3277
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Conventional MRI is frequently used during the diagnosis of multiple sclerosis but provides only little additional pathological information. Proton MRS ( 1 H‐MRS), however, provides biochemical information on the lesion pathology by visualization of a spectrum of metabolites. In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter. Therefore, we used the cuprizone model, a well‐established mouse model to mimic type III human multiple sclerosis demyelinating lesions. First, we identified CX3 CL1/CX3 CR1 signaling as a major regulator of microglial activity in the cuprizone mouse model. Compared with control groups (heterozygous CX3 CR1 +/− C57BL/6 mice and wild type CX3 CR1 +/+ C57BL/6 mice), microgliosis, astrogliosis, oligodendrocyte cell death and demyelination were shown to be highly reduced or absent in CX3 CR1 −/− C57BL/6 mice. Second, we show that 1 H‐MRS metabolite spectra are different when comparing cuprizone‐treated CX3 CR1 −/− mice showing mild demyelination with cuprizone‐treated CX3 CR1 +/+ mice showing severe demyelination and demyelination‐associated inflammation. Following cuprizone treatment, CX3 CR1 +/+ mice show a decrease in the Glu, tCho and tNAA concentrations as well as an increased Tau concentration. In contrast, following cuprizone treatment CX3 CR1 −/− mice only showed a decrease in tCho and tNAA concentrations. Therefore, 1 H‐MRS might possibly allow us to discriminate demyelination from demyelination‐associated inflammation via changes in Tau and Glu concentration. In addition, the observed decrease in tCho concentration in cuprizone‐induced demyelinating lesions should be further explored as a possible diagnostic tool for the early identification of human MS type III lesions. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : Microgliosis, astrogliosis, oligodendrocyte loss and demyelination were shown to be highly reduced or absent in CX3 CR1 ‐/‐ C57BL/6 mice compared to wild type CX3 CR1 +/+ C57BL/6 mice following a 4 week 0.2% cuprizone treatment. 1 H‐MRS showed differences in Tau and Glu concentration between cuprizone‐induced demyelination and demyelination associated inflammation. In addition, a decreased tCho concentration should be further explored as a diagnostical tool for the detection of type III multiple sclerosis lesions.