[Abstract Title]. - Society for Neuroscience

Poster
259. Cochlear Mechanoreceptors
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 259.10/BB6
Topic: D.02.a. Mechanoreceptors and cochlea
Support: NIH Grant CA21765
NIH Grant 1F31DC009393
ALSAC, Hartwell individual biomedical research award
NIH Grant DC008800
NIH Grant DC006471
Title: Effect of p16 Ink4a deletion on cochlear hair cells after damage with ototoxic drugs
Authors: *B. C. COX 1 , S. PAPAL 1 , K. A. STEIGELMAN 1,2 , J. ZUO 1 ;
1 Dev Neurobiol, St Jude Children's Res. Ho, Memphis, TN; 2 Anat. and Neurobio., Univ. of
Tennessee Hlth. Sci. Ctr., Memphis, TN
Abstract: Exposure to harmful noise or ototoxic drugs can induce hearing loss which is
primarily caused by damage to sensory hair cells of the inner ear. Humans and other mammals
cannot replace damaged hair cells; however, chicken, fish and amphibians can, by proliferation
and transdifferentiation of neighboring supporting cells. Based on non-mammalian models, we
hypothesize that mammalian hair cells release a signal when damaged that triggers supporting
cells to re-enter the cell cycle and later to transdifferentiate into hair cells. Unblocking the
inhibition of cell cycle re-entry in postmitotic, quiescent supporting cells appears to be the first
and most important step in this process. Recently, many researchers have studied hair cell
regeneration by manipulating the retinoblastoma protein as well as cyclin-dependent kinase
inhibitors. These studies have obtained mixed results depending on the timing and the cell-type
specificity of the gene deletion. The cyclin-dependant kinase inhibitor, p16 Ink4a, is not expressed
until animals are aged or have experienced an insult; thus, deletion of this protein is attractive as
it may allow supporting cells to respond to the signal naturally released by damaged hair cells.
We have recently begun studies with p16 Ink4a -null mice and found that these mice have normal
hearing and normal structure and morphology of the inner ear and hair cells. We are currently
conducting studies with ototoxic drugs (gentamicin and cisplatin) in p16 Ink4a -null mice and will