Cell cycle progression in gentamicin-damaged avian cochleas

Bhave, SA; Js, Stone; Rubel, EW; Coltrera,

doi:10.1523/jneurosci.15-06-04618.1995

Cited by 71 publications

(105 citation statements)

References 36 publications

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“…In chicks, a descending proximo-distal gradient of GTTR uptake, particularly in hair cells along the neural edge, is similar to the pattern of avian hair cell death following aminoglycoside treatment (Bhave et al, 1995;Cotanche et al, 1994;Hashino et al, 1995b). Recent studies show that noise-trauma can induce avian hair cell death processes within 3−6 h of insult (Mangiardi et al, 2004).…”

Section: Chicksmentioning

confidence: 72%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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Aminoglycoside uptake in the inner ear remains poorly understood. We subcutaneously injected a fluorescently-conjugated aminoglycoside, gentamicin-Texas Red (GTTR), to investigate the in vivo uptake of GTTR in the inner ear of several vertebrates, and in various murine sensory cells using confocal microscopy.In bullfrogs, GTTR uptake was prominent in mature hair cells, but not in immature hair cells. Avian hair cells accrued GTTR more rapidly at the base of the basilar papilla. GTTR was associated with the hair bundle; and, in guinea pigs and mice, somatic GTTR fluorescence was initially diffuse before punctate (endosomal) fluorescence could be observed. A baso-apical gradient of intracellular GTTR uptake in guinea pig cochleae could only be detected at early time points (<3 h). In 21−28 day mice, cochlear GTTR uptake was greatly reduced compared to guinea pigs, 6-day-old mice, or mice treated with ethacrynic acid. In mice, GTTR was also rapidly taken up, and retained, in the kidney, dorsal root and trigeminal ganglia. In linguinal and vibrissal tissues rapid GTTR uptake cleared over a period of several days.The preferential uptake of GTTR by mature saccular, and proximal hair cells resembles the pattern of aminoglycoside-induced hair cell death in bullfrogs and chicks. Differences in the degree of GTTR uptake in hair cells of different species suggests variation in serum levels, clearance rates from serum, and/or the developmental and functional integrity of the blood-labyrinth barrier. GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies.

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Section: Chicksmentioning

confidence: 72%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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“…In vivo, a few SCs in the BP enter S phase around 2 days after aminoglycoside treatment, and SC divi-sion peaks a day later (Bhave et al 1995(Bhave et al , 1998Stone et al 1999;Duncan et al 2006). To determine if SCs enter S phase on a similar schedule after streptomycin-induced HC damage in vitro, BrdU (1 µM) was added to culture media (DMEM/1% FBS) for 4 h at 1, 2, 3, 5, or 7 days in vitro, and cultures were fixed and immunolabeled for BrdU.…”

Section: Supporting Cell Reentry Into Cell Cycle After Aminoglycosidementioning

confidence: 99%

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Shang

Cafaro

Nehmer

et al. 2010

JARO

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In chickens, nonsensory supporting cells divide and regenerate auditory hair cells after injury. Anatomical evidence suggests that supporting cells can also transdifferentiate into hair cells without dividing. In this study, we characterized an organ culture model to study auditory hair cell regeneration, and we used these cultures to test if direct transdifferentiation alone can lead to significant hair cell regeneration. Control cultures (organs from posthatch chickens maintained without streptomycin) showed complete hair cell loss in the proximal (high-frequency) region by 5 days. In contrast, a 2-day treatment with streptomycin induced loss of hair cells from all regions by 3 days. Hair cell regeneration proceeded in culture, with the time course of supporting cell division and hair cell differentiation generally resembling in vivo patterns. The degree of supporting cell division depended upon the presence of streptomycin, the epithelial region, the type of culture media, and serum concentration. On average, 87% of the regenerated hair cells lacked the cell division marker BrdU despite its continuous presence, suggesting that most hair cells were regenerated via direct transdifferentiation. Addition of the DNA polymerase inhibitor aphidicolin to culture media prevented supporting cell division, but numerous hair cells were regenerated nonetheless. These hair cells showed signs of functional maturation, including stereociliary bundles and rapid uptake of FM1-43. These observations demonstrate that direct transdifferentiation is a significant mechanism of hair cell regeneration in the chicken auditory after streptomycin damage in vitro.

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“…To assess the temporal and spatial progression of differentiation of regenerated hair cells, chicks were administered a single intramuscular injection of tritiated thymidine ( 3 Hthymidine; 10 Ci/gm; 70 -90 Ci/mmol) or an intraperitoneal injection of bromodeoxyuridine (BrdU; 100 mg/kg) at 3 d after gentamicin injection, when cell proliferation is maximal (Bhave et al, 1995). Chicks were euthanized at 2, 24, 48, 72, or 240 hr (10 d) after injection of the S phase marker by an intraperitoneal injection of sodium pentobarbital, and whole mounts of the basilar papillae were removed and fixed.…”

Section: Immunohistochemistry Of Cochlear Whole Mountsmentioning

confidence: 99%

Hair Cell Differentiation in Chick Cochlear Epithelium after Aminoglycoside Toxicity:In VivoandIn VitroObservations

Leaño²,

et al. 1996

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Inner ear epithelia of mature birds regenerate hair cells after ototoxic or acoustic insult. The lack of markers that selectively label cells in regenerating epithelia and of culture systems composed primarily of progenitor cells has hampered the identification of cellular and molecular interactions that regulate hair cell regeneration. In control basilar papillae, we identified two markers that selectively label hair cells (calmodulin and TUJ1 ␤ tubulin antibodies) and one marker unique for support cells (cytokeratin antibodies). Examination of regenerating epithelia demonstrated that calmodulin and ␤ tubulin are also expressed in early differentiating hair cells, and cytokeratins are retained in proliferative support cells. Enzymatic and mechanical methods were used to isolate sensory epithelia from mature chick basilar papillae, and epithelia were cultured in different conditions. In control cultures, hair cells are morphologically stable for up to 6 d, because calmodulin immunoreactivity and phalloidin labeling of filamentous actin are retained. The addition of an ototoxic antibiotic to cultures, however, causes complete hair cell loss by 2 d in vitro and generates cultures composed of calmodulinnegative, cytokeratin-positive support cells. These cells are highly proliferative for the first 2-7 d after plating, but stop dividing by 9 d. Calmodulin-or TUJ1-positive cells reemerge in cultures treated with antibiotic for 5 d and maintained for an additional 5 d without antibiotic. A subset of calmodulinpositive cells was also labeled with BrdU when it was continuously present in cultures, suggesting that some cells generated in culture begin to differentiate into hair cells. Key words: hair cells; regeneration; chick; basilar papilla; cell culture; differentiationHair cells are sensory receptors for hearing, equilibrium, and motion detection. Some animals demonstrate the capacity to generate hair cells throughout their lifetime (Popper and Hoxter, 1984;Corwin, 1985; Jörgenson and Mathiessen, 1989;Roberson et al., 1992) or to initiate hair cell regeneration in the event of their loss (Corwin and Cotanche, 1988;Ryals and Rubel, 1988). The progenitors of hair cells seem to be a subset of support cells that reside adjacent to hair cells in the sensory epithelia (Girod et al., 1989;Balak et al., 1990;Raphael, 1992;Hashino and Salvi, 1993;Weisleder and Rubel, 1993;Stone and Cotanche, 1994;Tsue et al., 1994a;Roberson et al., 1996). Although mature mammals normally do not generate new hair cells, recent in vivo and in vitro studies have documented mitotic activity and immature-looking hair cells in mammalian vestibular epithelia after exposure to ototoxic drugs Warchol et al., 1993;Rubel et al., 1995), suggesting that hair cell regeneration in mammals may be inducible. The development of culture methods for mature cochlear and vestibular end organs has been initiated to identify molecules that regulate cell proliferation and differentiation in avian and mammalian hair cell epithelia. Co-culture experiments suggest that...

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Cell cycle progression in gentamicin-damaged avian cochleas

Cited by 71 publications

References 36 publications

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Hair Cell Differentiation in Chick Cochlear Epithelium after Aminoglycoside Toxicity:In VivoandIn VitroObservations

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