Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Glia. 2013 Jun;61(6):843-54. doi: 10.1002/glia.22476. Epub 2013 Mar 28.
Neuronal activity promotes myelination in vivo and in vitro. However, the molecular events that mediate activity-dependent myelination are not completely understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM) promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG) neurons and oligodendrocytes (OLs); the increase in myelination was frequency-dependent. Myelin segment formation was also enhanced following exposure of DRGs to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP) levels in DRGs were increased three-fold following ESTIM, and artificially increasing cAMP mimicked the ability of ESTIM to promote myelination. Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination. We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs and assessed cell-type specific effects of ESTIM on myelination. A selective increase or decrease in DRG cAMP levels resulted in enhanced or suppressed myelination, respectively. This work describes a novel role for the cAMP pathway in neurons that results in enhanced myelination.
神经元活动促进体内和体外的髓鞘形成。然而，介导活动依赖性髓鞘形成的分子事件尚不完全清楚。每周进行 7 次、每次 1 小时的模式化电刺激（ESTIM）可促进背根神经节（DRG）神经元和少突胶质细胞（OLs）混合培养物中髓鞘节段的形成；髓鞘形成与频率有关。在 OL 添加之前，DRG 暴露于 ESTIM 也可增强髓鞘形成，表明 ESTIM 以涉及神经元特异性信号的方式促进髓鞘形成。ESTIM 后 DRG 中的环磷酸腺苷（cAMP）水平增加了三倍，并且人工增加 cAMP 模拟了 ESTIM 促进髓鞘形成的能力。相反，抑制 cAMP 途径可抑制 ESTIM 诱导的髓鞘形成。我们使用分区式微流控平台将 DRG 体从 OLs 中分离出来，并评估了 ESTIM 对髓鞘形成的细胞类型特异性影响。DRG cAMP 水平的选择性增加或减少分别导致髓鞘形成增强或抑制。这项工作描述了 cAMP 途径在神经元中的新作用，导致髓鞘形成增强。
