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P75 神经生长因子受体可控制中风后脑室下区神经干细胞的迁移。

P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.

机构信息

Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Faculty of Biology, University of Freiburg, Freiburg, Germany.

出版信息

Cell Tissue Res. 2022 Mar;387(3):415-431. doi: 10.1007/s00441-021-03539-z. Epub 2021 Oct 26.

DOI:10.1007/s00441-021-03539-z
PMID:34698916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8975773/
Abstract

Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75 NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75 abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75 NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75 NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75 abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.

摘要

中风是成年人残疾的主要原因。内源性神经干细胞/祖细胞（NSPCs）来源于侧脑室下区（SVZ），有助于大脑修复过程。然而，中枢神经系统疾病诱导的 SVZ NSPC 向病变区域定向迁移的分子机制尚不清楚。在这里，我们发现，在小鼠中敲除 p75 神经营养因子受体（p75）可减少皮质损伤后 SVZ NSPC 向病变区域的迁移，并且 p75 NSPC 在体外 BDNF 刺激下无法迁移。皮质损伤通过骨形态发生蛋白（BMP）受体信号迅速增加 SVZ NSPC 中的 p75 丰度。SVZ 来源的 p75 NSPC 显示细胞骨架网络和小 GTPase 家族相关基因和蛋白表达的改变。相应地，与 BMP 处理的迁移野生型 NSPC 相比，BMP 处理的非迁移 p75 NSPC 显示出改变的形态和 α-微管蛋白表达。我们提出，BMP 诱导的 NSPC 中 p75 的丰度是通过调节皮质损伤后细胞骨架来调节 SVZ NSPC 向病变区域迁移的调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/c5528e1e40f7/441_2021_3539_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/e4bfe23c87b7/441_2021_3539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/779a29cc8f7e/441_2021_3539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/2aaa6f55901d/441_2021_3539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/42a27bec39c5/441_2021_3539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/2e5ccca3ab2d/441_2021_3539_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/d890d72e964b/441_2021_3539_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/c5528e1e40f7/441_2021_3539_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/e4bfe23c87b7/441_2021_3539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/779a29cc8f7e/441_2021_3539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/2aaa6f55901d/441_2021_3539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/42a27bec39c5/441_2021_3539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/2e5ccca3ab2d/441_2021_3539_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/d890d72e964b/441_2021_3539_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0f/8975773/c5528e1e40f7/441_2021_3539_Fig7_HTML.jpg

相似文献

[1]
P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.

Cell Tissue Res. 2022-3

[2]
Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling.

Nat Commun. 2020-1-31

[3]
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[4]
Cellular Response of Ventricular-Subventricular Neural Progenitor/Stem Cells to Neonatal Hypoxic-Ischemic Brain Injury and Their Enhanced Neurogenesis.

Yonsei Med J. 2020-6

[5]
p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells.

J Neurosci. 2007-5-9

[6]
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[7]
The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.

EMBO J. 2015-11-12

[8]
Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats.

J Neurosci. 2008-12-10

[9]
p75(NTR)-immunoreactivity in the subventricular zone of adult male rats: expression by cycling cells.

J Mol Histol. 2004-11

[10]
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引用本文的文献

[1]
Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy - A Comprehensive Literature Review.

Int J Nanomedicine. 2024

[2]
Differential contribution of TrkB and p75 to BDNF-dependent self-renewal, proliferation, and differentiation of adult neural stem cells.

Front Mol Neurosci. 2023-12-22

[3]
Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway.

Metab Brain Dis. 2023-8

[4]
Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease.

Front Cell Neurosci. 2023-4-5

[5]
Neurotrophins and Other Growth Factors in the Pathogenesis of Alzheimer's Disease.

Life (Basel). 2023-2-26

[6]
Endogenous Neural Stem Cell Activation after Low-Intensity Focused Ultrasound-Induced Blood-Brain Barrier Modulation.

Int J Mol Sci. 2023-3-16

[7]
Immunomodulatory and Anti-inflammatory effect of Neural Stem/Progenitor Cells in the Central Nervous System.

Stem Cell Rev Rep. 2023-5

[8]
Pointing fingers at blood contact: mechanisms of subventricular zone neural stem cell differentiation.

Neural Regen Res. 2023-1

[9]
Modulating scar formation for improving brain repair: from coagulation and inflammation to cell therapy.

Cell Tissue Res. 2022-3

本文引用的文献

[1]
In vivo functions of p75: challenges and opportunities for an emerging therapeutic target.

Trends Pharmacol Sci. 2021-9

[2]
p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound.

Cell Mol Neurobiol. 2022-5

[3]
Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling.

Nat Commun. 2020-1-31

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Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain.

Development. 2019-2-18

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Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Impairing Adult Neurogenesis.

Cell Rep. 2018-11-27

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Nucleic Acids Res. 2019-1-8

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Development. 2017-11-1

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Nat Methods. 2017-3-6

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Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke.

Cell Stem Cell. 2015-10-8

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