title: Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury.
abstract: 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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Kathren L
authors.initials: KL
authors.lastname: Fink
authors.affiliation: Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Francesc
authors.initials: F
authors.lastname: López-Giráldez
authors.affiliation: Department of Ophthalmology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: In-Jung
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: william.cafferty@yale.edu.
authors.forename: William B J
authors.initials: WBJ
authors.lastname: Cafferty
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D002490:Central Nervous System / Q000293:injuries* / Q000473:pathology*; D020869:Gene Expression Profiling; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D016501:Neurites / Q000378:metabolism; D055495:Neurogenesis; D011485:Protein Binding; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology; D014158:Transcription, Genetic
keywords: LPAR1; LPPR1; RNA-aseq; behavior; laser capture microdissection; plasticity; regeneration; spinal cord injury; μ-crystallin