Cited by 108Nerve injury and regenerationAxon Guidance and Neuronal SignalingGlaucoma and retinal disorders

Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS

Sapieha, Przemyslaw S., Duplan, Laure, Uetani, Noriko, Joly, Sandrine, Tremblay, Michel L., Kennedy, Timothy E., Di Polo, Adriana·2005·Molecular and Cellular Neuroscience

Abstract

Recently, receptor protein tyrosine phosphatase-sigma (RPTPsigma) has been shown to inhibit axon regeneration in injured peripheral nerves. Unlike the peripheral nervous system (PNS), central nervous system (CNS) neurons fail to regenerate their axons after injury or in disease. In order to assess the role of RPTPsigma in CNS regeneration, we used the retinocollicular system of adult mice lacking RPTPsigma to evaluate retinal ganglion cell (RGC) axon regrowth after optic nerve lesion. Quantitative analysis demonstrated a significant increase in the number of RGC axons that crossed the glial scar and extended distally in optic nerves from RPTPsigma (-/-) mice compared to wild-type littermate controls. Although we found that RPTPsigma is expressed by adult RGCs in wild-type mice, the retinas and optic nerves of adult RPTPsigma (-/-) mice showed no histological defects. Furthermore, the time-course of RGC death after nerve lesion was not different between knockout and wild-type animals. Thus, enhanced axon regrowth in the absence of RPTPsigma could not be attributed to developmental defects or increased neuronal survival. Finally, we show constitutively elevated activity of mitogen-activated protein kinase (MAPK) and Akt kinase in adult RPTPsigma (-/-) mice retinas, suggesting that these signaling pathways may contribute to promoting RGC axon regrowth following traumatic nerve injury. Our results support a model in which RPTPsigma inhibits axon regeneration in the adult injured CNS.

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Crossref · 10.1016/j.mcn.2004.10.011

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Authors
Sapieha, P. S., Duplan, L., Uetani, N., Joly, S., Tremblay, M. L., Kennedy, T. E., & Di Polo, A.
Affiliations
  • Université de Montréal (CA)
  • McGill University (CA)
  • Montreal Neurological Institute and Hospital (CA)
Venue
Molecular and Cellular Neuroscience
Publisher
Elsevier BV
Published
2005-04
Volume
28
Issue
4
Pages
625-635
ISSN
1044-7431 (ISSN-L)
OpenAlex
W2092811972
Cited by
106
References
76
Citations by year
2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 15 · 2013: 6 · 2012: 10
FWCI
1.45
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular and Cellular Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
Keywords
axon regeneration, optic nerve injury, retinal ganglion cells, glial scar, mitogen-activated protein kinase, Akt kinase, knockout mice
MeSH terms
Animals, Axons, Female, Mice, Inbred BALB C, Nerve Regeneration, Neural Inhibition, Retinal Ganglion Cells, Protein Tyrosine Phosphatases, Mice, Knockout, Optic Nerve Injuries, Mice, Receptor-Like Protein Tyrosine Phosphatases, Class 2

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