Journal of Neuroscience, Vol 15, 4618-4628, Copyright © 1995 by Society for Neuroscience
Cell cycle progression in gentamicin-damaged avian cochleas
SA Bhave, JS Stone, EW Rubel and MD Coltrera
Virginia Merrill Bloedel Hearing Research Center, Seattle, Washington, USA.
Hair cells, the sensory receptors of the auditory, vestibular, and
lateral-line organs, may be damaged by a number of agents including
aminoglycoside antibiotics and severe overstimulation. In the avian
cochlea, lost hair cells can be replaced by regeneration. These new hair
cells appear to be derived from a support cell precursor which is
stimulated to divide by events associated with hair cell loss. Little is
known about the timing and sequencing of events leading to new hair cell
production. In this study cell cycle-associated events in the avian cochlea
were analyzed at early and late time intervals following a single high dose
of gentamicin. This single dose protocol has been shown to consistently
result in extensive morphological damage and hair cell loss in the proximal
region of the cochlea while sparing a morphologically undamaged distal
cochlear region. This allowed for the differential analysis of the
underlying support cell populations with respect to local hair cell loss.
Three cell cycle associated markers were used to evaluate which cells
entered and progressed through the cell cycle: statin, a G0 associated
nuclear marker; proliferating cell nuclear antigen (PCNA), a G1, S and G2
associated marker; and 5- bromodeoxyuridine (BrdU), an S phase associated
marker. Using these markers we found evidence for reversible changes in
cell cycle status throughout the cochlea, while progression through S phase
and mitosis was restricted to the region of the cochlea which sustained
hair cell loss.