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Neuron. 2015 Jun 3;86(5):1215-27. doi: 10.1016/j.neuron.2015.05.005. Epub 2015 May 21.

Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS.

Author information

1
F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
2
Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
3
Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Neurology, David Geffen School of Medicine, and Multiple Myeloma Research Consortium, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Anaesthesia Department, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.costigan@childrens.harvard.edu.
6
F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: clifford.woolf@childrens.harvard.edu.

Abstract

Axon regeneration in the CNS requires reactivating injured neurons' intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater sprouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. Inhibition of Activin signaling in CAST/Ei mice diminishes their CNS regenerative capacity, whereas its activation in C57BL/6 animals boosts regeneration. This screen demonstrates that mammalian CNS regeneration can occur and reveals a molecular pathway that contributes to this ability.

PMID:
26004914
PMCID:
PMC4458182
DOI:
10.1016/j.neuron.2015.05.005
[Indexed for MEDLINE]
Free PMC Article

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