Overexpression of Bcl-2 or Bcl-xL prevents spiral ganglion neuron death and inhibits neurite growth.
Spiral ganglion neurons (SGNs) provide afferent innervation to the cochlea and rely on contact with hair cells (HCs) for their survival. Following deafferentation due to hair cell loss, SGNs gradually die. In a rat culture model, we explored the ability of prosurvival members of the Bcl-2 family of proteins to support the survival and neurite outgrowth of SGNs. We found that overexpression of either Bcl-2 or Bcl-xL significantly increases SGN survival in the absence of neurotrophic factors, establishing that the Bcl-2 pathway is sufficient for SGN cell survival and that SGN deprived of trophic support die by an apoptotic mechanism. However, in contrast to observations in central neurons and PC12 cells where Bcl-2 appears to promote neurite growth, both Bcl-2 and Bcl-xL overexpression dramatically inhibit neurite outgrowth in SGNs. This inhibition of neurite growth by Bcl-2 occurs in nearly all SGNs even in the presence of multiple neurotrophic factors implying that Bcl-2 directly inhibits neurite growth rather than simply rescuing a subpopulation of neurons incapable of extending neurites without additional stimuli. Thus, although overexpression of prosurvival members of the Bcl-2 family prevents SGN loss following trophic factor deprivation, the inhibition of neurite growth by these molecules may limit their efficacy for support of auditory nerve maintenance or regeneration following hair cell loss.
Hansen
Marlan R
MR
Department of Otolaryngology, Head, and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA. marlan-hansen@uiowa.edu
Roehm
Pamela C
PC
Xu
Ningyong
N
Green
Steven H
SH
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D013136:Spiral Ganglion / Q000166:cytology*; D014162:Transfection; D051020:bcl-X Protein / Q000378:metabolism*
C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D049452:Green Fluorescent Proteins