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
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
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DOI：
10.1016/j.neuroimage.2013.07.080
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发表时间：
2014-02-01
期刊：
影响因子：
5.7
通讯作者：
Van der Linden, Annemie
中科院分区：
文献类型：
--
作者：
Guglielmetti, Caroline;Praet, Jelle;Van der Linden, Annemie
多发性硬化症是一种毁灭性的中枢神经系统(CNS)脱髓鞘疾病，在这种疾病中，内源性再髓鞘作用经常失败，从而导致康复。虽然Cuprizones小鼠模型允许阐明许多控制重新髓鞘形成的分子因素，但目前对在该模型中启动重新髓鞘形成的少突胶质前体细胞的空间起源知之甚少。因此，我们在这个模型中研究了脑室下区(SVZ)神经干细胞/祖细胞(NSPC)是否参与了铜酮诱导的脱髓鞘后压部的重新髓鞘形成。实验上，从NSPC原位标记之日起，C57BL/6J小鼠连续4周饲喂0.2%的铜酮饲料，然后按正常饮食恢复8周。采用两种原位标记策略：(I)通过脑室注射微米级氧化铁颗粒标记NSPC，然后通过磁共振成像(MRI)进行纵向追踪；(Ii)将编码EGFP和荧光素酶报告蛋白的慢病毒载体转导SVZ NSPC，通过体内生物发光成像(BLI)进行纵向监测。与前面的建议相反，在MRI和BLI中没有观察到SVZ NSPC向脱髓鞘压部的迁移，并通过组织学分析进一步验证，从而表明SVZ NSPC不能直接促进铜带模型中压髓的重新髓鞘形成。有趣的是，使用纵向BLI分析并经组织学分析证实，观察到在铜必利酮治疗后SVZ NSPC来源的神经母细胞向嗅球迁移的增加，这表明CNS炎症和增加的神经发生之间存在潜在的联系。(C)2013年提交人。爱思唯尔公司出版，版权所有。
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 demyelinadon. 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 8 weeks. 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. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.