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Inhibition of the c‐Jun N‐Terminal Kinase Signaling Pathway Influences Neurite Outgrowth of Spiral Ganglion Neurons In Vitro
Author(s) -
Bodmer Daniel,
Gloddek Bertrand,
Ryan Allen F.,
Huverstuhl Jochen,
Brors Dominik
Publication year - 2002
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200211000-00028
Subject(s) - neurite , in vitro , microbiology and biotechnology , spiral ganglion , terminal (telecommunication) , chemistry , kinase , biology , neuroscience , anatomy , biochemistry , computer science , telecommunications , inner ear
Objectives Inhibitors of the c‐Jun N‐terminal kinase (JNK) signaling pathway have been demonstrated to protect hair cells of the auditory system and different types of neurons from various insults, and their use for future therapeutic applications has been proposed. In the study, we evaluated the effects of inhibition of the JNK pathway on process outgrowth from spiral ganglion neurons. Methods Spiral ganglion explants from rats (postnatal days 3–5) that were cultured on laminin were treated with neurotrophin‐3 and/or the JNK signaling pathway inhibitor CEP‐11004. Both neurite length and number of the explants were evaluated and statistically analyzed by analysis of variance. Results Inhibition of the JNK signaling pathway reduced process outgrowth from spiral ganglion explants. The reduction, both in length and number of neurites, was reversed by the application of neurotrophin‐3. Conclusions The results indicate that an intact JNK signaling pathway is important for process outgrowth of spiral ganglion neurons. However, neurotrophin‐3 stimulates process extension by a JNK independent pathway. Our results demonstrate that inhibition of the JNK pathway can have adverse effects on the extension of spiral ganglion neurons, but that the negative effects can be ameliorated by appropriate treatment.