P75 Neurotrophin Receptor Controls Subventricular Zone Neural Stem Cell Migration After Stroke

Overview

Journal Cell Tissue Res

Specialties Anatomy & Histology
Cell Biology

Date 2021 Oct 26

PMID 34698916

Citations 9

Authors

Sachin S Deshpande

Subash C Malik

Pasquale Conforti

Jia-Di Lin

Yu-Hsuan Chu

Suvra Nath

Franziska Greulich

Meike-Ast Dumbach

N Henriette Uhlenhaut

Christian Schachtrup

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Schachtrup C, Ryu J, Helmrick M, Vagena E, Galanakis D, Degen J . Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage. J Neurosci. 2010; 30(17):5843-54. PMC: 2871011. DOI: 10.1523/JNEUROSCI.0137-10.2010. View

Faiz M, Sachewsky N, Gascon S, Bang K, Morshead C, Nagy A . Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke. Cell Stem Cell. 2015; 17(5):624-34. DOI: 10.1016/j.stem.2015.08.002. View

Labat-Gest V, Tomasi S . Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies. J Vis Exp. 2013; (76). PMC: 3727176. DOI: 10.3791/50370. View

Reynolds B, Weiss S . Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992; 255(5052):1707-10. DOI: 10.1126/science.1553558. View

Domeniconi M, Zampieri N, Spencer T, Hilaire M, Mellado W, Chao M . MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth. Neuron. 2005; 46(6):849-55. DOI: 10.1016/j.neuron.2005.05.029. View

Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O . Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke. 2007; 38(11):3032-9. DOI: 10.1161/STROKEAHA.107.488445. View

Lee K, Li E, Huber L, Landis S, Sharpe A, Chao M . Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell. 1992; 69(5):737-49. DOI: 10.1016/0092-8674(92)90286-l. View

Benner E, Luciano D, Jo R, Abdi K, Paez-Gonzalez P, Sheng H . Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature. 2013; 497(7449):369-73. PMC: 3667629. DOI: 10.1038/nature12069. View

Pous L, Deshpande S, Nath S, Mezey S, Malik S, Schildge S . Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling. Nat Commun. 2020; 11(1):630. PMC: 6994610. DOI: 10.1038/s41467-020-14466-y. View

10.

Ohab J, Fleming S, Blesch A, Carmichael S . A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006; 26(50):13007-16. PMC: 6674957. DOI: 10.1523/JNEUROSCI.4323-06.2006. View

11.

Irmady K, Jackman K, Padow V, Shahani N, Martin L, Cerchietti L . Mir-592 regulates the induction and cell death-promoting activity of p75NTR in neuronal ischemic injury. J Neurosci. 2014; 34(9):3419-28. PMC: 3935094. DOI: 10.1523/JNEUROSCI.1982-13.2014. View

12.

Colditz M, Catts V, Al-menhali N, Osborne G, Bartlett P, Coulson E . p75 neurotrophin receptor regulates basal and fluoxetine-stimulated hippocampal neurogenesis. Exp Brain Res. 2009; 200(2):161-7. DOI: 10.1007/s00221-009-1947-6. View

13.

Durinck S, Spellman P, Birney E, Huber W . Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc. 2009; 4(8):1184-91. PMC: 3159387. DOI: 10.1038/nprot.2009.97. View

14.

Schachtrup C, Ryu J, Mammadzada K, Khan A, Carlton P, Perez A . Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-β signaling and astrocyte functions. Nat Neurosci. 2015; 18(8):1077-80. PMC: 4878404. DOI: 10.1038/nn.4054. View

15.

Wanner I, Anderson M, Song B, Levine J, Fernandez A, Gray-Thompson Z . Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci. 2013; 33(31):12870-86. PMC: 3728693. DOI: 10.1523/JNEUROSCI.2121-13.2013. View

16.

Massague J, Seoane J, Wotton D . Smad transcription factors. Genes Dev. 2005; 19(23):2783-810. DOI: 10.1101/gad.1350705. View

17.

Dechant G, Barde Y . The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci. 2002; 5(11):1131-6. DOI: 10.1038/nn1102-1131. View

18.

Cunningham F, Achuthan P, Akanni W, Allen J, Amode M, Armean I . Ensembl 2019. Nucleic Acids Res. 2018; 47(D1):D745-D751. PMC: 6323964. DOI: 10.1093/nar/gky1113. View

19.

Zywitza V, Misios A, Bunatyan L, Willnow T, Rajewsky N . Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Impairing Adult Neurogenesis. Cell Rep. 2018; 25(9):2457-2469.e8. DOI: 10.1016/j.celrep.2018.11.003. View

20.

Peterson S, Bogenmann E . Osmotic swelling induces p75 neurotrophin receptor (p75NTR) expression via nitric oxide. J Biol Chem. 2003; 278(36):33943-50. DOI: 10.1074/jbc.M302376200. View