Journal article
Influence of cAMP and protein kinase A on neurite length from spiral ganglion neurons
Hearing research, Vol.283(1-2), pp.33-44
01/2012
DOI: 10.1016/j.heares.2011.11.010
PMCID: PMC3277666
PMID: 22154930
Abstract
Regrowth of peripheral spiral ganglion neuron (SGN) fibers is a primary objective in efforts to improve cochlear implant outcomes and to potentially reinnervate regenerated hair cells. Cyclic adenosine monophosphate (cAMP) regulates neurite growth and guidance via activation of protein kinase A (PKA) and
E
xchange
P
rotein directly
A
ctivated by
C
ylic AMP (Epac). Here we explored the effects of cAMP signaling on SGN neurite length
in vitro
. We find that the cAMP analog, cpt-cAMP, exerts a biphasic effect on neurite length; increasing length at lower concentrations and reducing length at higher concentrations. This biphasic response occurs in cultures plated on laminin, fibronectin, or tenascin C suggesting that it is not substrate dependent. cpt-cAMP also reduces SGN neurite branching. The Epac-specific agonist, 8-pCPT-2’-O-Me-cAMP, does not alter SGN neurite length. Constitutively active PKA isoforms strongly inhibit SGN neurite length similar to higher levels of cAMP. Chronic membrane depolarization activates PKA in SGNs and also inhibits SGN neurite length. However, inhibition of PKA fails to rescue neurite length in depolarized cultures implying that activation of PKA is not necessary for the inhibition of SGN neurite length by chronic depolarization. Expression of constitutively active phosphatidylinositol 3-kinase, but not c-Jun N-terminal kinase, isoforms partially rescues SGN neurite length in the presence of activated PKA. Taken together, these results suggest that activation of cAMP/PKA represents a potential strategy to enhance SGN fiber elongation following deafness; however such therapies will likely require careful titration so as to simultaneously promote rather than inhibit nerve fiber regeneration.
Details
- Title: Subtitle
- Influence of cAMP and protein kinase A on neurite length from spiral ganglion neurons
- Creators
- Ningyong Xu - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242Jonathan Engbers - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242Sobia Khaja - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242Linjing Xu - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242J. Jason Clark - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242Marlan R Hansen - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Hearing research, Vol.283(1-2), pp.33-44
- DOI
- 10.1016/j.heares.2011.11.010
- PMID
- 22154930
- PMCID
- PMC3277666
- NLM abbreviation
- Hear Res
- ISSN
- 0378-5955
- eISSN
- 1878-5891
- Grant note
- R01 DC009801-01A1 || DC / National Institute on Deafness and Other Communication Disorders : NIDCD K08 DC006211-01A1 || DC / National Institute on Deafness and Other Communication Disorders : NIDCD P30 DC010362-01A1 || DC / National Institute on Deafness and Other Communication Disorders : NIDCD
- Language
- English
- Date published
- 01/2012
- Academic Unit
- Molecular Physiology and Biophysics; Neurosurgery; Otolaryngology
- Record Identifier
- 9984007191002771
Metrics
17 Record Views