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

Cell Rep. 2017 Mar 14;18(11):2687-2701. doi: 10.1016/j.celrep.2017.02.058.


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.

Keywords: LPAR1; LPPR1; RNA-aseq; behavior; laser capture microdissection; plasticity; regeneration; spinal cord injury; μ-crystallin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology*
  • Central Nervous System / injuries*
  • Central Nervous System / pathology*
  • Gene Expression Profiling
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / pathology
  • Neurites / metabolism
  • Neurogenesis
  • Protein Binding
  • Signal Transduction
  • Spinal Cord / pathology
  • Transcription, Genetic