Journal article
Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo
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.
Language: | English |
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Year: | 2012 |
Pages: | 172-181 |
ISSN: | 0531559x , 00144886 and 10902430 |
Types: | Journal article |
DOI: | 10.1016/j.expneurol.2011.09.027 |
ORCIDs: | 0000-0003-0316-5866 |
Amino Acid Sequence Animals Animals, Newborn Cell Movement Cell Survival Cells, Cultured Central Nervous System Cerebral Ventricles Chromatography, High Pressure Liquid Cloning, Molecular Culture Media, Conditioned Deafness Disease Models, Animal Dose-Response Relationship, Drug Doublecortin Domain Proteins Embryo, Mammalian Enzyme Inhibitors Female Gene Expression Regulation, Developmental Guinea Pigs Humans In Vitro Techniques Male Mice Microscopy, Electron, Scanning Microtubule-Associated Proteins Neomycin Nerve Growth Factors Nerve Tissue Proteins Neural Stem Cells Neurites Neurons Neuropeptides Rats Spiral Ganglion Tandem Mass Spectrometry Transfection cometin protein, mouse meteorin protein, mouse