Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures

Ding, Dalian; Salvi, Richard; Roth, Jerome A.

doi:10.1007/s12640-015-9538-8

Cited by 25 publications

(23 citation statements)

References 49 publications

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“…Hair cell loss was quantified using as epifluorescence Zeiss Axioskop microscope (400×) with appropriate filters for detecting Alexa Fluor‐488 conjugated phalloidin in the hair cell stereocilia and cuticular plate. As described in detail in earlier publications, counts of all of the IHC and OHC were made over 0.24 mm segments over the entire length of the cochlea from apex to base (Ding et al, ; Ding et al, ; Fu et al, ; Li et al, ). HC counts were used to construct a cochleogram for each culture showing the percent IHC and OHC loss as a function of percent distance from the apex along the length of the cochlea.…”

Section: Methodsmentioning

confidence: 99%

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Carbaryl-induced ototoxicity in rat postnatal cochlear organotypic cultures

et al. 2016

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Carbaryl, a widely used carbamate-based insecticide, is a potent anticholinesterase known to induce delayed neurotoxicity following chronic exposure. However, its potential toxic effects on the cochlea, the sensory organ for hearing that contains cholinergic efferent neurons and acetylcholine receptors on the hair cells (HC) and spiral ganglion neurons has heretofore not been evaluated. To assess ototoxic potential of carbaryl, cochlear organotypic cultures from postnatal day 3 rats were treated with doses of carbaryl ranging from 50 to 500 μM for 48 h up to 96 h. Carbaryl damaged both the sensory HC and spiral ganglion neurons in a dose- and duration-dependent manner. HC and neuronal damage was observed at carbaryl concentrations as low as 50 μM after 96-h treatment and 100 μM after 48-h treatment. Hair cell was greatest in the high frequency basal region of the cochlea and progressively decreased towards the apex consistent with the majority of ototoxic drugs. In contrast, damage to the spiral ganglion neurons was of similar magnitude in the basal and apical regions of the cochlea. Carbaryl damage was characterized by soma shrinkage, nuclear condensation and fragmentation, and blebbing, morphological features of programmed cell death. Carbaryl upregulated the expression of executioner caspase-3 in HC and spiral ganglion neurons indicating that cellular damage occurred primarily by caspase-mediated apoptosis. These results suggest that chronic exposure to carbaryl and other carbamate anticholinesterases may be ototoxic. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 956-969, 2017.

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Section: Methodsmentioning

confidence: 99%

“…The data was analyzed statistically using one‐way analysis of variance (GraphPad Prism 5) and Newman–Keuls post‐hoc analysis as described previously (Li et al, ).…”

Section: Methodsmentioning

confidence: 99%

Carbaryl-induced ototoxicity in rat postnatal cochlear organotypic cultures

et al. 2016

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“…Cochlear hair cells are the primary receptors in the inner ear that perceive sound-induced vibrations. Cochlear hair cell loss is one of the common causes of permanent sensorineural deafness and is caused by ototoxic drugs, heavy metal poisoning, high-intensity noise, pesticide poisoning, and other factors (Ding et al 2012 ; Li et al 2015 ; Prakash Krishnan Muthaiah et al 2017 ; Yu et al 2015 ). Surface preparations of the cochlea and basilar membrane (BM) must be prepared to count hair cells and generate a cochleogram to quantitatively evaluate the extent of cochlear hair cell loss in different locations along the entire length of the cochlear BM.…”

Section: Introductionmentioning

confidence: 99%

Cochlear hair cell densities in the rabbit

et al. 2018

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A typical cochleogram was plotted to investigate hair cell densities as a percentage along the whole length of the basilar membrane (BM) of the rabbit, the length of the BM and the width of the organ of Corti. We generated surface preparations of cochlea from adult, healthy New Zealand White (NZW) rabbits. The numbers of inner hair cells (IHCs) and outer hair cells (OHCs) were counted from images acquired from a digital camera attached to an Olympus light microscope with a scale of 100 μm as a primary unit drawn continuously, and the numbers of IHCs and OHCs were converted to densities at 10% intervals along the length of the cochlea. Meanwhile, the length of the BM and the width of the organ of Corti were calculated. The average length of the cochlea was 14.504 ± 0.403 mm, while the total number of IHCs and the numbers of OHCs in the first, second, and third rows were 1556 ± 13, 1840 ± 47, 1842 ± 46, and 1840 ± 45, respectively, accounting for 21.98%, 26.00%, 26.02%, and 26.00% of the total number of cells, respectively. The densities of each row of OHCs reported in 10% intervals were greater than the densities of the IHCs corresponding to their anatomical locations within the cochlea. The densities of OHCs in each row were distributed uniformly along the BM, while the IHCs densities were not and showed a bimodal distribution with a maximum density at the apex and at 70–80% of the cochlear length from the apex but a lower density in the remaining cochlea. The width of the organ of Corti decreased successively from the apex to the base.

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“…In high concentrations, cobalt can also trigger cell death after entering the hair cells of the lateral line (Becker, 2013) or the mammalian cochlea (Li et al, 2015; Lee et al, 2016). The mechanisms for the death of hair cells and associated neurons from high concentrations of cobalt exposure are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

A non-toxic dose of cobalt chloride blocks hair cells of the zebrafish lateral line

2017

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Experiments on the flow-sensitive lateral line system of fishes have provided important insights into the function and sensory transduction of vertebrate hair cells. A common experimental approach has been to pharmacologically block lateral line hair cells and measure how behavior changes. Cobalt chloride (CoCl2) blocks the lateral line by inhibiting calcium movement through the membrane channels of hair cells, but high concentrations can be toxic, making it unclear whether changes in behavior are due to a blocked lateral line or poor health. Here, we identify a non-toxic treatment of cobalt that completely blocks lateral line hair cells. We exposed 5-day post fertilization zebrafish larvae to CoCl2 concentrations ranging from 1–20 mM for 15 minutes and measured 1) the spiking rate of the afferent neurons contacting hair cells and 2) the larvae’s health and long-term survival. Our results show that a 15-minute exposure to 5 mM CoCl2 abolishes both spontaneous and evoked afferent firing. This treatment does not change swimming behavior, and results in >85% survival after 5 days. Weaker treatments of CoCl2 did not eliminate afferent activity, while stronger treatments caused close to 50% mortality. Our work provides a guideline for future zebrafish investigations where physiological confirmation of a blocked lateral line system is required.

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Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures

Cited by 25 publications

References 49 publications

Carbaryl-induced ototoxicity in rat postnatal cochlear organotypic cultures

Carbaryl-induced ototoxicity in rat postnatal cochlear organotypic cultures

Cochlear hair cell densities in the rabbit

A non-toxic dose of cobalt chloride blocks hair cells of the zebrafish lateral line

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