Reactive oxygen species mediate activity-dependent neuron-glia signaling in output fibers of the hippocampus
Reactive oxygen species mediate activity-dependent neuron-glia signaling in output fibers of the hippocampus
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DOI：
10.1523/jneurosci.19-17-07241.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Sweatt, JD
中科院分区：
文献类型：
--
作者：
Atkins, CM;Sweatt, JD
非突触信号在神经系统活动依赖性变化的研究中越来越受到重视。我们研究了引起海马输出纤维中神经元和神经胶质细胞之间非突触通讯的神经元活动类型。高频率，但不是低频率，动作电位发射在有髓鞘的海马CA 1轴突导致少突胶质细胞特异性蛋白髓鞘碱性蛋白（MBP）的磷酸化增加。这种变化被河豚毒素阻断，表明轴突产生的动作电位是调节MBP磷酸化状态所必需的。此外，清除剂的活性氧物种超氧化物和过氧化氢和一氧化氮合酶抑制剂防止激活的神经元神经胶质细胞信号通路。这些结果表明，在海马CA 1区的神经元活动增加的时期，产生活性氧和氮物质，其扩散到邻近的少突胶质细胞，并导致髓鞘中的关键结构蛋白MBP的翻译后修饰。因此，除了它们众所周知的活动依赖性神经元-神经元信号传导能力之外，海马锥体神经元还具有活动依赖性神经元-神经胶质信号传导机制。
Nonsynaptic signaling is becoming increasingly appreciated in studies of activity-dependent changes in the nervous system. We investigated the types of neuronal activity that elicit nonsynaptic communication between neurons and glial cells in hippocampal output fibers. High-frequency, but not low-frequency, action potential firing in myelinated CA1 axons of the hippocampus resulted in increased phosphorylation of the oligodendrocyte-specific protein myelin basic protein (MBP). This change was blocked by tetrodotoxin, indicating that axonally generated action potentials were necessary to regulate the phosphorylation state of MBP. Furthermore, scavengers of the reactive oxygen species superoxide and hydrogen peroxide and nitric oxide synthase inhibitors prevented activation of this neuron-glia signaling pathway. These results indicate that, during periods of increased neuronal activity in area CA1 of the hippocampus, reactive oxygen and nitrogen species are generated, which diffuse to neighboring oligodendrocytes and result in post-translational modifications of MBP, a key structural protein in myelin. Thus, in addition to their well-known capacity for activity-dependent neuron-neuron signaling, hippocampal pyramidal neurons possess a mechanism for activity-dependent neuron-glia signaling.