PDF(Pubmed)
Abstract：
In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS.
摘要：
在多发性硬化症（MS）患者中，新生和存活的少突胶质细胞（OL）可以促进髓鞘再生，然而,目前的疗法无法增强或维持内源性修复。低强度重复经颅磁刺激(LI-rTMS),作为间歇性θ爆发刺激(iTBS)递送，增加健康成年小鼠皮质中新生OLs的存活和成熟，但目前尚不清楚LI-rTMS是否能促进髓鞘再生.为了检查这种可能性，我们在成年小鼠大脑中荧光标记了少突胶质细胞祖细胞（OPCs;Pdgfrα-CreER转基因小鼠）或成熟的OLs（Plp-CreER转基因小鼠），并追踪了每个细胞群体随时间的命运。iTBS每日疗程（600脉冲；120mT），在Cuprizone（CPZ）喂养期间交付，不会改变新的或预先存在的OL生存率，但增加了初级运动皮层（M1）中新的OL修饰的髓鞘节间数。这导致每个新的M1OL产生约471µm的髓鞘。当LI-rTMS在CPZ戒断后(在髓鞘再生期间)交付时,它显着增加了新的M1和call骨OLs制作的节间长度，增加了支持call体（CC）节间的存活OL的数量，并增加了有髓鞘的轴突的比例。LI-rTMS改变皮质神经元活动的能力以及新的和存活的OLs的行为，表明它可能是一种合适的辅助干预措施，以增强MS患者的髓鞘再生。
