Background Oligodendrocytes are myelinating cells of the central nervous system which support functionally, structurally, and metabolically neurons. of -tubulin. Conclusions Mature oligodendrocytes acutely increase their cytoskeletal plasticity during demyelination. They are therefore not passive players under demyelinating conditions but can rather react dynamically to external insults. imaging, CNS plasticity, Cytoskeletal dynamics Background Oligodendrocytes (ODCs) are cells of the central nervous system (CNS) whose processes form myelin, a multi-layered membrane structure participating in saltatory transmission conduction  and metabolic support of neuronal axons [2,3]. Myelin Sirt7 is usually produced in the last developmental stage of ODCs through a rapid, tightly regulated process  in which overlaying contiguous membranes become strongly interconnected by extruding cytoplasm to form compact myelin . These membrane domains remain directly connected to the cell body with a complex underlying cytoarchitecture comprising microtubules distributed in larger processes and actin filaments enriched in thinner myelin domains and in paranodes [6,7]. -actin and -tubulin are thus main players in dynamics of axon targeting and myelin stability [7,8]. Acute or chronic damage to ODCs inevitably prospects to neuronal loss as observed in several animal models [9-11] and human diseases such as multiple sclerosis (MS) and inherited leukodystrophies of the CNS . However, demyelination and ODC death also lead to the activation of oligodendrocyte progenitor cells (OPCs) [11-15]. These cells can develop into mature ODCs and remyelinate naked axons, thus restoring saltatory conduction . In this context, the role of surviving mature ODCs within and surrounding damaged CNS areas is still unclear. While it is usually Limonin cost current dogma that mature ODCs lack the ability to remyelinate axons [13,17], some studies indicate that these cells can at least maintain different degrees of structural plasticity. Earlier observations in different experimental paradigms and within MS lesions show sparse mature ODC proliferation within remyelinating areas [18-20], and ODCs can survive match attack by actively shedding myelin vesicles , regenerate myelin processes after damage [22,23], and display migratory capability after maturation . Also, the fact that ODCs close to or within neuroinflammatory lesions that have been deprived of their myelin processes can survive this insult [25,26] suggests the presence of active mechanisms of cellular plasticity. Insights into dynamic properties of ODCs could come from the study of the cell cytoarchitecture which regulates and drives membrane movements . In order to investigate Limonin cost the plasticity of mature ODCs under demyelinating conditions after injection of luciferin. We followed bioluminescence changes in two experimental models of ODC damage, namely diphtheria toxin (DTx)-mediated ODC killing (oDTR model [11,29,30]), and in the neuroinflammatory paradigm experimental autoimmune encephalomyelitis (EAE) . oLucR mice revealed defined and reproducible increases in the bioluminescence during induced demyelination in both experimental paradigms, independently from ODC generation from progenitors. The measured and bioluminescence correlated with the longitudinal data, indicating that our observations revealed an intrinsic feature of the damaged ODC populace. Transcriptional analysis of structural genes in the damaged CNS and specifically within ODCs showed increased expression of cytoskeleton genes after demyelinating insult. Our results thus elaborate in a novel model previous suggestions that ODCs undergoing/sensing cellular stress can transiently enhance their own plasticity [21-24]; furthermore, we provide important insights around the timing and extent of such activation in experimental demyelination models. Methods Animals Mice were kept under SPF conditions according to Swiss and German animal laws and institutional guidelines. Animal experiments were conducted under the license figures 13/2006 and 55.2-1-54-2532-1-12 after approval by the respective Swiss and German government companies, the of the Canton of Zurich as well as the  (WT 350?bp) GAC AAT TCA GAG TGA TAG GAC CAG GGT ATC CC and GCT GCC TAT TAT TGG TAA GAG TGG; (knock-in, 700?bp) TCC AAT TTA CTG ACC GTA CAC and Kitty CAG CTA CAC CAG AGA CGG AAA TC;  (WT 600?bp, KI 845?bp) AAA GTC Limonin cost GCT CTG AGT TGT TAT, GGA GCG GGA GAA ATG GAT AAA GTC GCT CTG AGT TGT TAT, GGA GCG GGA GAA ATG GAT ATG, and AAT AGG AAC TTC GTC GAG AAT AGG AAC TTC GTC GAG C; (415?bp).