Central nervous system remyelination in culture--a tool for multiple sclerosis research.
Bottom Line: This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease.Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money.We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies.
Affiliation: MS Centre, Centre for Regenerative Medicine, University of Edinburgh, Queen's Medical Research Centre, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK.Show MeSH
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Mentions: We considered the possibility that the apparent return of myelin sheaths in our slice system represents myelination of previously unmyelinated nerve fibres. Remyelinated myelin sheaths are thinner and have shorter internodal lengths compared to myelin sheaths formed in development (Perier and Gregoire, 1965; Prineas and Connell, 1979). To investigate whether the return of myelin sheaths after LPC treatment represents genuinely remyelinated fibres, we performed electron microscopy on cerebellar slices, to measure G-ratios (Figs. 4A–C). Myelinated fibres were measured after 10 DIV and “remyelinated” fibres at 25 DIV, with demyelination on day 10. The G ratio represents the ratio of the diameter of the axon to the diameter of the myelinated fibre and allows comparison of myelin thickness for different axon sizes. There was a marked difference between the groups, with “remyelinated” fibres having higher G ratios and thus thinner myelin sheaths. The curves of best fit through the points are shown in Fig. 4D, and these are statistically significantly different using the maximum likelihood ratio test (p < 0.05).
Affiliation: MS Centre, Centre for Regenerative Medicine, University of Edinburgh, Queen's Medical Research Centre, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK.