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Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum.

Abstract
Multiple sclerosis is a devastating demyelinating disease of the central nervous system (CNS) in which endogenous remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8weeks. Two in situ labeling strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis, an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis.
AuthorsCaroline Guglielmetti, Jelle Praet, Janaki Raman Rangarajan, Ruth Vreys, Nathalie De Vocht, Frederik Maes, Marleen Verhoye, Peter Ponsaerts, Annemie Van der Linden
JournalNeuroImage (Neuroimage) Vol. 86 Pg. 99-110 (Feb 01 2014) ISSN: 1095-9572 [Electronic] United States
PMID23933305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013.
Chemical References
  • Cuprizone
Topics
  • Animals
  • Cell Movement
  • Cell Tracking (methods)
  • Cerebral Ventricles (pathology)
  • Corpus Callosum (pathology)
  • Cuprizone
  • Demyelinating Diseases (chemically induced, pathology)
  • Diffusion Magnetic Resonance Imaging (methods)
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence (methods)
  • Multimodal Imaging (methods)
  • Nerve Fibers, Myelinated (pathology)
  • Neural Pathways (pathology)
  • Neural Stem Cells (pathology)
  • Neurogenesis
  • Olfactory Bulb (pathology)

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