Regulation of myelin structure and conduction velocity by perinodal astrocytes.
Regulation of myelin structure and conduction velocity by perinodal astrocytes.
复制标题
DOI：
10.1073/pnas.1811013115
复制
发表时间：
2018-11-13
影响因子：
11.1
通讯作者：
Fields RD
中科院分区：
文献类型：
--
作者：
Dutta DJ;Woo DH;Lee PR;Pajevic S;Bukalo O;Huffman WC;Wake H;Basser PJ;SheikhBahaei S;Lazarevic V;Smith JC;Fields RD
大脑各区域之间通过白质束进行适当的交流，使我们能够完成复杂的认知和运动任务。为了使这种通信有效，脉冲必须几乎同时到达中继点。髓磷脂能实现脉冲的跃变传导，因此是脉冲传导速度调制的候选物质。但是髓磷脂结构一旦形成，就被认为是静态的。在这项研究中，我们发现成熟髓鞘结构是动态的。成熟髓鞘厚度和节隙长度可以可逆调节，从而优化轴突脉冲的速度。这种髓磷脂的调节是由凝血酶蛋白酶抑制剂在朗维耶结的星形胶质细胞的胞吐调节的。脉冲传递的速度对于神经回路的最佳功能至关重要，但目前尚不清楚如何在单个轴突中建立适当的传导速度。脉冲传输速度受髓鞘厚度和沿轴突的Ranvier电结形态的影响。在这里，我们发现髓鞘厚度和淋巴结间隙长度被星形胶质细胞可逆地改变，星形胶质细胞是接触兰维耶淋巴结的胶质细胞。凝血酶依赖性蛋白水解是一种将髓磷脂附着在轴突上的细胞粘附分子（神经束蛋白155），凝血酶蛋白酶抑制剂从结周星形胶质细胞囊状释放后可以抑制这种分子的蛋白水解。在星形胶质细胞中表达VAMP2的显性阴性片段的转基因小鼠，可以减少50%的胞吐，表现出与轴突相邻的髓鞘副神经环脱离，节间隙长度增加，视神经髓鞘变薄。这些形态变化改变了轴突的被动电缆特性，减少了传导速度和到达中枢神经系统的峰值时间，同时降低了视力。所有的效果被凝血酶抑制剂Fondaparinux逆转。用破伤风毒素转染大鼠胼胝体星形胶质细胞获得了类似的结果。在此之前，髓鞘是如何变薄的尚不清楚，而且对结周星形胶质细胞的功能也不甚了解。这些发现描述了一种神经系统可塑性的形式，其中髓鞘结构和传导速度由星形胶质细胞调节。凝血酶依赖性的神经束蛋白155的分裂也可能与髓磷脂的破坏和修复有关。
Proper communication between brain regions, via white matter tracts, allows us to carry out complex cognitive and motor tasks. Impulses traveling must arrive at relay points almost simultaneously for such communication to be effective. Myelin enables saltatory conduction of impulses and hence is a candidate for modulation of impulse conduction velocity. But myelin structure, once formed, has been considered static. In this study, we show that mature myelin structure is dynamic. The mature myelin sheath thickness and nodal gap length can be reversibly modulated to optimize the speed of axonal impulses. This modulation of myelin is regulated by exocytosis of thrombin protease inhibitors from astrocytes at the node of Ranvier. The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impulse transmission is influenced by the thickness of the myelin sheath and the morphology of electrogenic nodes of Ranvier along axons. Here we show that myelin thickness and nodal gap length are reversibly altered by astrocytes, glial cells that contact nodes of Ranvier. Thrombin-dependent proteolysis of a cell adhesion molecule that attaches myelin to the axon (neurofascin 155) is inhibited by vesicular release of thrombin protease inhibitors from perinodal astrocytes. Transgenic mice expressing a dominant-negative fragment of VAMP2 in astrocytes, to reduce exocytosis by 50%, exhibited detachment of adjacent paranodal loops of myelin from the axon, increased nodal gap length, and thinning of the myelin sheath in the optic nerve. These morphological changes alter the passive cable properties of axons to reduce conduction velocity and spike-time arrival in the CNS in parallel with a decrease in visual acuity. All effects were reversed by the thrombin inhibitor Fondaparinux. Similar results were obtained by viral transfection of tetanus toxin into astrocytes of rat corpus callosum. Previously, it was unknown how the myelin sheath could be thinned and the functions of perinodal astrocytes were not well understood. These findings describe a form of nervous system plasticity in which myelin structure and conduction velocity are adjusted by astrocytes. The thrombin-dependent cleavage of neurofascin 155 may also have relevance to myelin disruption and repair.
登录
查看更多内容
DOI：
10.1126/science.aan6203
发表时间：
2017-10-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Khodagholy D;Gelinas JN;Buzsáki G
通讯作者：
Buzsáki G
影响因子：
16.2
作者：
Buzsáki G;Logothetis N;Singer W
通讯作者：
Singer W
影响因子：
9.2
作者：
Charles, P;Tait, S;Lubetzki, C
通讯作者：
Lubetzki, C
影响因子：
8
作者：
Gucek, Alenka;Jorgacevski, Jernej;Zorec, Robert
通讯作者：
Zorec, Robert
DOI：
10.1097/01.jnen.0000196133.74087.cb
发表时间：
2006-01-01
影响因子：
3.2
作者：
Arai, T;Miklossy, J;McGeer, PL
通讯作者：
McGeer, PL