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

Publication date: 14 March 2017
Source:Cell Reports, Volume 18, Issue 11
Author(s): Kathren L. Fink, Francesc López-Giráldez, In-Jung Kim, Stephen M. Strittmatter, William B.J. Cafferty
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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Fink et al. present an original in vivo screen identifying targets that drive spontaneous functional plasticity in intact corticospinal motor neurons after CNS injury. They show that exploitation of one of the targets identified (LPAR1-LPPR1 axis) results in significant anatomical and functional recovery after adult SCI.


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