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成年大鼠髓磷脂增强神经干细胞的轴突生长。

Adult rat myelin enhances axonal outgrowth from neural stem cells.

机构信息

Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.

Departments of Psychiatry and Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Sci Transl Med. 2018 May 23;10(442). doi: 10.1126/scitranslmed.aal2563.


DOI:10.1126/scitranslmed.aal2563
PMID:29794059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8377986/
Abstract

Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell-derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal-regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.

摘要

脊髓损伤 (SCI) 后轴突再生受到与髓鞘相关的生长抑制分子的抑制。我们报告说,大鼠髓鞘刺激了移植到成年大鼠 SCI 部位的大鼠神经祖细胞 (NPC) 中出现的轴突的生长。当在髓鞘底物上培养时,大鼠 NPC 和人诱导多能干细胞 (iPSC) 衍生的神经干细胞 (NSC) 的突起生长增加了三倍。在体内,大鼠 NPC 和人 iPSC 衍生的 NSC 通过成年中枢神经系统白质延伸的轴突数量多于通过灰质延伸的轴突数量,并且优先与大鼠宿主髓鞘相关。机制研究排除了 Nogo 受体信号作为髓鞘对干细胞衍生轴突生长反应的介导物。对啮齿动物 NPC 的转录组筛选鉴定出细胞粘附分子神经元生长调节剂 1 (Negr1) 作为允许轴突-髓鞘相互作用的一种介导物。髓鞘相关蛋白对啮齿动物 NPC 的刺激作用受发育调控,涉及细胞外信号调节激酶 (ERK) 的直接激活。髓鞘对 NPC/NSC 轴突生长的刺激作用应进一步研究,并可能在 SCI 后神经修复中得到利用。

相似文献

[1]
Adult rat myelin enhances axonal outgrowth from neural stem cells.

Sci Transl Med. 2018-5-23

[2]
Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons.

eNeuro. 2017-2-3

[3]
Myelination of axons emerging from neural progenitor grafts after spinal cord injury.

Exp Neurol. 2017-10

[4]
Erythropoietin-mediated preservation of the white matter in rat spinal cord injury.

Neuroscience. 2007-2-9

[5]
CNS axon regeneration inhibitors stimulate an immediate early gene response via MAP kinase-SRF signaling.

Mol Brain. 2014-11-19

[6]
Upregulation of axon guidance molecules in the adult central nervous system of Nogo-A knockout mice restricts neuronal growth and regeneration.

Eur J Neurosci. 2013-9-16

[7]
Epac2 Elevation Reverses Inhibition by Chondroitin Sulfate Proteoglycans and Transforms Postlesion Inhibitory Environment to Promote Axonal Outgrowth in an Model of Spinal Cord Injury.

J Neurosci. 2019-8-13

[8]
Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon regeneration in vivo.

J Neurosci. 2015-3-11

[9]
Myelin basic protein enhances axonal regeneration from neural progenitor cells.

Cell Biosci. 2021-4-29

[10]
Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate.

J Neurosci. 2001-7-1

引用本文的文献

[1]
Biological engineering approaches for modulating the pathological microenvironment and promoting axonal regeneration after spinal cord injury.

Front Neurosci. 2025-5-12

[2]
Developmental and neurobehavioral toxicity of benzotriazole ultraviolet stabilizer UV-360 on zebrafish larvae.

PLoS One. 2025-5-23

[3]
Role of exercise on ncRNAs and exosomal ncRNAs in preventing neurodegenerative diseases: a narrative review.

Mol Med. 2025-2-7

[4]
Exosomes as promising bioactive materials in the treatment of spinal cord injury.

Stem Cell Res Ther. 2024-9-27

[5]
Clickable Granular Hydrogel Scaffolds for Delivery of Neural Progenitor Cells to Sites of Spinal Cord Injury.

Adv Healthc Mater. 2024-10

[6]
Differences in Anatomical Outcomes Between Early Chronic and Far Chronic Time-Points After Transplantation of Spinal Cord Neural Progenitor Cells in Mice.

J Neurotrauma. 2023-12

[7]
Regulation of axonal regeneration after mammalian spinal cord injury.

Nat Rev Mol Cell Biol. 2023-6

[8]
Cell transplantation to repair the injured spinal cord.

Int Rev Neurobiol. 2022

[9]
The Role of Biomaterials in Peripheral Nerve and Spinal Cord Injury: A Review.

Int J Mol Sci. 2022-1-23

[10]
Motor neuron replacement therapy for amyotrophic lateral sclerosis.

Neural Regen Res. 2022-8

本文引用的文献

[1]
Restorative effects of human neural stem cell grafts on the primate spinal cord.

Nat Med. 2018-2-26

[2]
Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.

Nat Commun. 2018-1-8

[3]
Myelination of axons emerging from neural progenitor grafts after spinal cord injury.

Exp Neurol. 2017-10

[4]
Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration.

Nat Med. 2016-5

[5]
The IgLON Family Member Negr1 Promotes Neuronal Arborization Acting as Soluble Factor via FGFR2.

Front Mol Neurosci. 2016-1-13

[6]
Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury.

Neuron. 2014-8-20

[7]
PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system.

Nat Commun. 2014-4-1

[8]
Switching responses: spatial and temporal regulators of axon guidance.

Mol Neurobiol. 2014-4

[9]
STAR: ultrafast universal RNA-seq aligner.

Bioinformatics. 2012-10-25

[10]
Long-distance growth and connectivity of neural stem cells after severe spinal cord injury.

Cell. 2012-9-14

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