Hair cell regeneration after streptomycin toxicity in the avian vestibular epithelium

Weisleder, Pedro; Rubel, Edwin W.

doi:10.1002/cne.903310106

Cited by 145 publications

(157 citation statements)

References 52 publications

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“…For example, in chicks the VCR was reported to have recovered by 2-3 weeks following systemic administrations of streptomycin, a significantly shorter time course than that observed for head stability in our adult pigeons (Goode et al 1999). However, in chicks, the total horizontal semicircular canal hair cell density was noted to be near normal values (Goode et al 1999), although type I hair cells remained reduced in number (Goode et al 1999;Weisleder and Rubel 1993). In contrast, in pigeons regenerating following intralabyrinthine streptomycin applications, hair cell densities were reported to be only 30% of normal in the otolith organs , similar to the qualitative SEM hair cell density counts observed in the present study.…”

Section: Behavioral Recovery During Regenerationmentioning

confidence: 58%

“…These extrastriola and peripheral regions in birds have a much higher concentration of type II receptor cells compared with type I cells ( . Type II cells have repeatedly been shown to regenerate faster than type I cells (Carey et al 1996;Goode et al 1999;Kevetter et al 2000;Masetto and Correia 1997;Weisleder and Rubel 1993).…”

Section: Vestibular Receptor Damage and Regenerationmentioning

confidence: 99%

“…With systemic injections, vestibular receptor cells were greatly diminished but nearly 35%-40% of the semicircular canal cells often remained intact (Carey et al 1996;Goode et al 1999;Matsui et al 2003). In the utricle, systemic injections typically damaged on even smaller percentage of cells (Lindeman 1969;Matsui et al 2003;Weisleder and Rubel 1993;Wersäll and Hawkins 1962). Thus, the observed recoveries in chicks were likely not due to regeneration alone but were coupled with possible remaining function of nondamaged hair cells as well as the rescue and repair of sublethally damaged hair cells (Baird et al 2002).…”

Section: Initial Vestibular Dysfunction Following Streptomycin Applicmentioning

confidence: 99%

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Posture, Head Stability, and Orientation Recovery During Vestibular Regeneration In Pigeons

Dickman

Lim

2004

JARO

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Compensatory behavior such as oculomotor, gaze, and postural responses that occur during movement largely depend upon a functioning vestibular system. In the present study, the initial loss and subsequent recovery of postural and head stability in pigeons undergoing vestibular regeneration were examined. Adult pigeons were trained to manipulate a straight run chamber to peck an illuminated key for fluid reward. Six behavioral measures assessing performance, posture, and head stability were quantified. These included run latency, steps (walking), path negotiation (lane changes), gaze saccades, head bobs, and head shakes. Once normative values were obtained for four birds, complete lesion of all receptor cells and denervation of the epithelia in the vestibular endorgans were produced using a single intralabyrinthine application of streptomycin sulfate. Each bird was then tested at specific times during regeneration and the same behavioral measures examined. At 7 days post-streptomycin treatment (PST), all birds exhibited severe postural and head instability, with tremors, head shakes, staggering, and circling predominating. No normal trial runs, walking, gaze saccades, or head bobs were present. Many of these dysfunctions persisted through 3-4 weeks PST. Gradually, tremor and head shakes diminished and were replaced with an increasing number of normal head bobs during steps and gaze saccades. Beginning at 4 weeks PST, but largely inaccurate, was the observed initiation of directed steps, less staggering, and some successful path negotiation. As regeneration progressed, spatial orientation and navigation ability increased and, by 49 days PST, most trials were successful. By 70 days PST, all birds had recovered to pretreatment levels. Thus, it was observed that ataxia must subside, coincident with normalized head and postural stability prior to the recovery of spatial orientation and path navigation recovery. Parallels in recovery were drawn to hair cell regeneration and afferent responsiveness, as inferred from present results and those in other investigations.

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Section: Behavioral Recovery During Regenerationmentioning

confidence: 58%

Section: Vestibular Receptor Damage and Regenerationmentioning

confidence: 99%

Section: Initial Vestibular Dysfunction Following Streptomycin Applicmentioning

confidence: 99%

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Posture, Head Stability, and Orientation Recovery During Vestibular Regeneration In Pigeons

Dickman

Lim

2004

JARO

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“…Several previous studies have demonstrated ongoing cell proliferation in mature vestibular organs (Jørgensen and Mathiesen, 1988;Roberson et al, 1992;Weisleder and Rubel, 1993;Rubel et al, 1995;Kil et al, 1997;Wilkins et al, 1999) and have demonstrated that the baseline level of proliferation appears to be counterbalanced by ongoing hair cell death (Kil et al, 1997;Goodyear et al, 1999;Stone et al, 1999;Wilkins et al, 1999). This dynamic pattern of ongoing cell death and proliferation differs from that observed in the chicken cochlea, in which the supporting cells are mitotically quiescent until the hair cells are lost because of trauma (Corwin and Cotanche, 1988; or proliferate at a very low rate .…”

Section: Relationship Between Spontaneous Hair Cell Death and Ongoingmentioning

confidence: 95%

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

2002

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Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment.Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dosedependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

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“…Hair cells dying in an apoptotic-like manner participate in an active, organized cellular degradation and disposal with preserved tissue integrity and minimal inflammatory response (Li et al 1995;Lang and Liu 1997;Forge and Li 2000). Such preservation of the architecture of the sensory epithelium (SE) is crucial in order to retain organ function, particularly in tissues where hair cells are continuously produced throughout life (Weisleder and Rubel 1993;Kil et al 1997;Williams and Holder 2000).…”

Section: Introductionmentioning

confidence: 99%

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cheng

Cunningham

Rubel

2003

JARO - Journal of the Association for Research in Otolaryngolog

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Caspases are a family of proteases that have been implicated as key mediators of cell death. Although nonspecific inhibition of caspase activation has been reported to prevent mammalian sensory hair cell death, the exact roles of individual caspases during hair cell death are unclear. In other systems, the activation of initiator caspases, such as caspase-8 and caspase-9, can lead to the activation of the effector caspase-3. We have begun to systematically characterize hair cell death in an in vitro system by examining the activation of these specific caspases in degenerating hair cells after acutely damaging the whole avian basilar papilla with gentamicin. Basilar papillae (BP) displayed a dose-dependent hair cell loss after a 24-h treatment with gentamicin at concentrations of 0.1, 0.5, and 2.0 mM. When treated with 0.5 mM gentamicin for 6, 12, or 24 h, hair cells first began to degenerate in the basal third of the BP and damage progressed apically. Supplementation of z-VAD-fmk, a general caspase inhibitor, provided short-term protection against gentamicin-induced hair cell death. Treatment with gentamicin for 6 or 12 h promoted the expression of active caspase-3 and active caspase-9 in many hair cells along the BP as shown by immunohistochemistry. At these timepoints, specific fluorescent-labeled peptide substrates detected more active caspase-3, caspase-8, and caspase-9 in gentamicin-treated hair cells relative to controls. Our data indicate that auditory hair cells degenerate as a result of gentamicin exposure in a caspase-dependent manner. Specifically, the upstream caspases, caspase-8 and caspase-9, and the downstream caspase-3 are activated in aminoglycoside-damaged hair cells.

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Hair cell regeneration after streptomycin toxicity in the avian vestibular epithelium

Cited by 145 publications

References 52 publications

Posture, Head Stability, and Orientation Recovery During Vestibular Regeneration In Pigeons

Posture, Head Stability, and Orientation Recovery During Vestibular Regeneration In Pigeons

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

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