Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782521331964706816 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5389739 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT finkkathrenl identificationofintrinsicaxongrowthmodulatorsforintactcnsneuronsafterinjury AT lopezgiraldezfrancesc identificationofintrinsicaxongrowthmodulatorsforintactcnsneuronsafterinjury AT kiminjung identificationofintrinsicaxongrowthmodulatorsforintactcnsneuronsafterinjury AT strittmatterstephenm identificationofintrinsicaxongrowthmodulatorsforintactcnsneuronsafterinjury AT caffertywilliambj identificationofintrinsicaxongrowthmodulatorsforintactcnsneuronsafterinjury |