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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

Guglielmetti, Caroline; Praet, Jelle; Rangarajan, Janaki Raman; Vreys, Ruth; De Vocht, Nathalie; Maes, Frederik; Verhoye, Marleen; Ponsaerts, Peter; Van der Linden, Annemie


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    <dct:title>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</dct:title>
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    <dct:description>&lt;p&gt;Multiple sclerosis is a devastating demyelinating disease of the central nervous system(CNS) in which endogenous&amp;nbsp;remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular&amp;nbsp;factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte&amp;nbsp;progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether&amp;nbsp;subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following&amp;nbsp;cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed&amp;nbsp;a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8 weeks. Two in situ labeling&amp;nbsp;strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide&amp;nbsp;particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs&amp;nbsp;were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring&amp;nbsp;by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ&amp;nbsp;NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological&amp;nbsp;analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the&amp;nbsp;splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis,&amp;nbsp;an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following&amp;nbsp;cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis.&lt;/p&gt;</dct:description>
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