Sox2 up-regulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear.
In the present study, glial cell responses to spiral ganglion neuron (SGN) degeneration were evaluated using a murine model of auditory neuropathy. Ouabain, a well-known Na,K-ATPase inhibitor, has been shown to induce SGN degeneration while sparing hair cell function. In addition to selectively removing type I SGNs, ouabain leads to hyperplasia and hypertrophy of glia-like cells in the injured auditory nerves. As the transcription factor Sox2 is predominantly expressed in proliferating and undifferentiated neural precursors during neurogenesis,we sought to examine Sox2 expression patterns following SGN injury by ouabain. Real-time RT-PCR and Western blot analyses of cochlea indicated a significant increase in Sox2 expression by 3 days posttreatment with ouabain. Cells incorporating bromodeoxyuridine(BrdU) and expressing Sox2 were counted in the auditory nerves of control and ouabain-treated ears. The glial phenotype of Sox2+cells was identified by two neural glial markers: S100 and Sox10. The number of Sox2+ glial cells significantly increased at 3 days post-treatment and reached its maximum level at 7 days post-treatment. Similarly,the number of BrdU+ cells increased at 3 and 7 days post-treatment in the injured nerves. Quantitative analysis with dual-immunostaining procedures indicated that about 70% of BrdU+ cells in the injured nerves were Sox2+ glial cells. These results demonstrate that up-regulation of Sox2 expression is associated with increased cell proliferation in the auditory nerve after injury.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Avenue, Charleston, SC 29425, USA. langh@musc.edu
Hainan
H
Lang
Manna
M
Li
Lauren A
LA
Kilpatrick
Juhong
J
Zhu
Devadoss J
DJ
Samuvel
Edward L
EL
Krug
John C
JC
Goddard
D000818:Animals; D049109:Cell Proliferation; D003056:Cochlear Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000294:innervation*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006313:Hearing Loss, Central / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology*; D010042:Ouabain / Q000009:adverse effects / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D004791:Enzyme Inhibitors; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D010042:Ouabain