Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo
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Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo. / Jørgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone; Thompson, Lachlan H; Houchins, Jeffrey P; Andrade, Nuno; Torp, Malene; Kalkkinen, Nisse; Andersson, Elisabet; Lindvall, Olle; Ulfendahl, Mats; Brunak, Søren; Johansen, Teit E; Wahlberg, Lars U.
In: Experimental Neurology, Vol. 233, No. 1, 2012, p. 172-81.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo
AU - Jørgensen, Jesper Roland
AU - Fransson, Anette
AU - Fjord-Larsen, Lone
AU - Thompson, Lachlan H
AU - Houchins, Jeffrey P
AU - Andrade, Nuno
AU - Torp, Malene
AU - Kalkkinen, Nisse
AU - Andersson, Elisabet
AU - Lindvall, Olle
AU - Ulfendahl, Mats
AU - Brunak, Søren
AU - Johansen, Teit E
AU - Wahlberg, Lars U
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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 1a. 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.
AB - 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 1a. 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.
KW - Amino Acid Sequence
KW - Animals
KW - Animals, Newborn
KW - Cell Movement
KW - Cell Survival
KW - Cells, Cultured
KW - Central Nervous System
KW - Cerebral Ventricles
KW - Chromatography, High Pressure Liquid
KW - Cloning, Molecular
KW - Culture Media, Conditioned
KW - Deafness
KW - Disease Models, Animal
KW - Dose-Response Relationship, Drug
KW - Embryo, Mammalian
KW - Enzyme Inhibitors
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Guinea Pigs
KW - Humans
KW - Male
KW - Mice
KW - Microscopy, Electron, Scanning
KW - Microtubule-Associated Proteins
KW - Neomycin
KW - Nerve Growth Factors
KW - Nerve Tissue Proteins
KW - Neural Stem Cells
KW - Neurites
KW - Neurons
KW - Neuropeptides
KW - Rats
KW - Spiral Ganglion
KW - Tandem Mass Spectrometry
KW - Transfection
U2 - 10.1016/j.expneurol.2011.09.027
DO - 10.1016/j.expneurol.2011.09.027
M3 - Journal article
C2 - 21985865
VL - 233
SP - 172
EP - 181
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -
ID: 40804197