Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

Research output: Contribution to journalArticle

Abstract

Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor la. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential. (C) 2011 Elsevier Inc. All rights reserved.

Details

Authors
  • Jesper Roland Jorgensen
  • Anette Fransson
  • Lone Fjord-Larsen
  • Lachlan H. Thompson
  • Jeffrey P. Houchins
  • Nuno Andrade
  • Malene Torp
  • Nisse Kalkkinen
  • Elisabet Andersson
  • Olle Lindvall
  • Mats Ulfendahl
  • Soren Brunak
  • Teit E. Johansen
  • Lars U. Wahlberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Floor plate, Meteorin, Migration, Neurotrophic, Trophic factor, Spiral, ganglion, Novel protein
Original languageEnglish
Pages (from-to)172-181
JournalExperimental Neurology
Volume233
Issue number1
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes