Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia.
Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia.
复制标题
通过联合调控GPR17和小胶质细胞诱导再生轴突的稳健髓鞘形成
DOI：
10.1016/j.neuron.2020.09.016
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发表时间：
2020-12-09
期刊：
影响因子：
16.2
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Wang J;He X;Meng H;Li Y;Dmitriev P;Tian F;Page JC;Lu QR;He Z
髓鞘形成促进快速轴突传导，从而使神经系统不同部分之间的有效通信成为可能。在这里，我们研究了中枢神经系统（CNS）损伤后和轴突再生过程中控制髓鞘形成的机制。以前，我们发现了多种分子途径和策略，可以促进视神经损伤后轴突再生。然而，再生的轴突仍然是无髓鞘的，其潜在的机制是难以捉摸的。在这项研究中，我们发现在受损的视神经中，少突胶质前体细胞（OPCs）经历短暂的增殖，但未能分化为成熟的髓鞘形成少突胶质细胞，这让人想起在人类进行性多发性硬化症中观察到的情况。从机制上讲，我们发现OPC内在的GPR17信号传导和小胶质细胞的持续激活都抑制了OPC分化的不同阶段。重要的是，GPR17和小胶质细胞的共同操纵导致再生轴突的广泛髓鞘形成。这里揭示的阶段依赖性OPC分化的调节机制表明CNS损伤后有效的从头髓鞘形成的可翻译策略。
Myelination facilitates rapid axonal conduction thereby enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and during axon regeneration in the central nervous system (CNS). Previously we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. However, regenerated axons remain unmyelinated and the underlying mechanisms were elusive. In this study, we found that in injured optic nerves, oligodendrocyte precursor cells (OPCs) undergo transient proliferation, but fail to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what is observed in human progressive multiple sclerosis. Mechanistically, we showed that both OPC-intrinsic GPR17 signaling and sustained activation of microglia inhibit different stages of OPC differentiation. Importantly, co-manipulation of GPR17 and microglia led to extensive myelination of regenerated axons. The regulatory mechanisms of stage-dependent OPC differentiation uncovered here suggest a translatable strategy for efficient de novo myelination after CNS injury.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
5.3
作者：
Abiraman, Kavitha;Pol, Suyog U.;Sim, Fraser J.
通讯作者：
Sim, Fraser J.
影响因子：
64.8
作者：
Hubler Z;Allimuthu D;Bederman I;Elitt MS;Madhavan M;Allan KC;Shick HE;Garrison E;T Karl M;Factor DC;Nevin ZS;Sax JL;Thompson MA;Fedorov Y;Jin J;Wilson WK;Giera M;Bracher F;Miller RH;Tesar PJ;Adams DJ
通讯作者：
Adams DJ
DOI：
10.1056/nejmoa1803583
发表时间：
2018-08-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fox RJ;Coffey CS;Conwit R;Cudkowicz ME;Gleason T;Goodman A;Klawiter EC;Matsuda K;McGovern M;Naismith RT;Ashokkumar A;Barnes J;Ecklund D;Klingner E;Koepp M;Long JD;Natarajan S;Thornell B;Yankey J;Bermel RA;Debbins JP;Huang X;Jagodnik P;Lowe MJ;Nakamura K;Narayanan S;Sakaie KE;Thoomukuntla B;Zhou X;Krieger S;Alvarez E;Apperson M;Bashir K;Cohen BA;Coyle PK;Delgado S;Dewitt LD;Flores A;Giesser BS;Goldman MD;Jubelt B;Lava N;Lynch SG;Moses H;Ontaneda D;Perumal JS;Racke M;Repovic P;Riley CS;Severson C;Shinnar S;Suski V;Weinstock-Guttman B;Yadav V;Zabeti A;NN102/SPRINT-MS Trial Investigators
通讯作者：
NN102/SPRINT-MS Trial Investigators
影响因子：
64.5
作者：
Bei F;Lee HHC;Liu X;Gunner G;Jin H;Ma L;Wang C;Hou L;Hensch TK;Frank E;Sanes JR;Chen C;Fagiolini M;He Z
通讯作者：
He Z