Abstract
In multiple sclerosis patients, chronic clinical deficits are known to result from axonal degeneration which is triggered by inadequate remyelination. The underlying molecular mechanisms of remyelination and its failure remain currently unclear. In vivo models, among the cuprizone model, are valuable tools to study underlying mechanisms of remyelination and its failure. Since complete and reproducible demyelination of the analyzed brain region is an indispensable prerequisite for efficient remyelination experiments, in this study we systematically addressed which part of the corpus callosum is reliably and consistently demyelinated after acute cuprizone-induced demyelination. Following a novel evaluation strategy, we can show that at the level of the rostral hippocampus, the most medial sectors of the corpus callosum (spanning 500 μm in the horizontal plane) are consistently demyelinated, whereas more lateral sectors show inconsistent and incomplete demyelination. These results precisely define a part of the corpus callosum which should be used as a region of interest during remyelination experiments.
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References
Cao J, Hu Y, Shazeeb MS, Pedraza CE, Pande N, Weinstock D, Polites GH, Zhang W, Chandross KJ, Ying X (2018) In vivo optical imaging of myelination events in a myelin basic protein promoter-driven luciferase transgenic mouse model. ASN Neuro 10:1759091418777329. https://doi.org/10.1177/1759091418777329
de Paula Faria D, de Vries EF, Sijbesma JW, Dierckx RA, Buchpiguel CA, Copray S (2014) PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C]CIC and [11C]MeDAS. Neuroimage 87:395–402. https://doi.org/10.1016/j.neuroimage.2013.10.057
Hochstrasser T, Exner GL, Nyamoya S, Schmitz C, Kipp M (2017) Cuprizone-containing pellets are less potent to induce consistent demyelination in the Corpus Callosum of C57BL/6 mice. J Mol Neurosci: MN 61:617–624. https://doi.org/10.1007/s12031-017-0903-3
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717
Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Bruck W, Lucchinetti C, Lassmann H (2006) Remyelination is extensive in a subset of multiple sclerosis patients. Brain 129:3165–3172. https://doi.org/10.1093/brain/awl217
Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137–151. https://doi.org/10.1002/ana.410330203
Schmidt T, Awad H, Slowik A, Beyer C, Kipp M, Clarner T (2013) Regional heterogeneity of cuprizone-induced demyelination: topographical aspects of the midline of the corpus callosum. J Mol Neurosci: MN 49:80–88. https://doi.org/10.1007/s12031-012-9896-0
Slowik A, Schmidt T, Beyer C, Amor S, Clarner T, Kipp M (2015) The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination. Br J Pharmacol 172:80–92. https://doi.org/10.1111/bph.12938
Stidworthy MF, Genoud S, Suter U, Mantei N, Franklin RJ (2003) Quantifying the early stages of remyelination following cuprizone-induced demyelination. Brain Pathol (Zurich, Switzerland) 13:329–339
Werneburg S, Fuchs HLS, Albers I, Burkhardt H, Gudi V, Skripuletz T, Stangel M, Gerardy-Schahn R, Hildebrandt H (2017) Polysialylation at early stages of oligodendrocyte differentiation promotes myelin repair. J Neurosci 37:8131–8141. https://doi.org/10.1523/jneurosci.1147-17.2017
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Chrzanowski, U., Schmitz, C., Horn-Bochtler, A. et al. Evaluation strategy to determine reliable demyelination in the cuprizone model. Metab Brain Dis 34, 681–685 (2019). https://doi.org/10.1007/s11011-018-0375-3
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DOI: https://doi.org/10.1007/s11011-018-0375-3