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Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury

Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact ci...

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Autores principales: Fink, Kathren L., López-Giráldez, Francesc, Kim, In-Jung, Strittmatter, Stephen M., Cafferty, William B.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389739/
https://www.ncbi.nlm.nih.gov/pubmed/28297672
http://dx.doi.org/10.1016/j.celrep.2017.02.058
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author Fink, Kathren L.
López-Giráldez, Francesc
Kim, In-Jung
Strittmatter, Stephen M.
Cafferty, William B.J.
author_facet Fink, Kathren L.
López-Giráldez, Francesc
Kim, In-Jung
Strittmatter, Stephen M.
Cafferty, William B.J.
author_sort Fink, Kathren L.
collection PubMed
description Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.
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spelling pubmed-53897392017-04-12 Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury Fink, Kathren L. López-Giráldez, Francesc Kim, In-Jung Strittmatter, Stephen M. Cafferty, William B.J. Cell Rep Article Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation. 2017-03-14 /pmc/articles/PMC5389739/ /pubmed/28297672 http://dx.doi.org/10.1016/j.celrep.2017.02.058 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Fink, Kathren L.
López-Giráldez, Francesc
Kim, In-Jung
Strittmatter, Stephen M.
Cafferty, William B.J.
Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title_full Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title_fullStr Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title_full_unstemmed Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title_short Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
title_sort identification of intrinsic axon growth modulators for intact cns neurons after injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389739/
https://www.ncbi.nlm.nih.gov/pubmed/28297672
http://dx.doi.org/10.1016/j.celrep.2017.02.058
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