A Mouse Model Validates the Utility of Electrocochleography in Verifying Endolymphatic Hydrops

Melki, Sami; Li, Yiping; Semaan, Maroun T.; Zheng, Qing Yin; Megerian, Cliff A.; Alagramam, Kumar N.

doi:10.1007/s10162-014-0445-0

Cited by 12 publications

(10 citation statements)

References 41 publications

(57 reference statements)

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“…Multiple studies have characterized the postnatal development and disease manifestations in the Phex mouse [7,9,23,24,30,31]. At birth, the mice have normal inner ear histology including no ELH, spiral ganglion degeneration, or endolymphatic duct obstruction.…”

Section: Methodsmentioning

confidence: 99%

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Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

Wick

Lin

et al. 2017

American Journal of Otolaryngology

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Hypothesis: Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). Background: Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice’s postnatal development of ELH and SNHL. Methods: Four cohortswere studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol frompostnatal day (P) 7–P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. Results: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. Conclusion: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.

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Section: Methodsmentioning

confidence: 99%

“…Radiographic studies have also demonstrated dysmorphic temporal bones [21,22]. All of the otologic manifestations associated with XLH in humans have been replicated in the Phex mouse model, particularly the presence of diseased otic capsule bone and ELH [7,23]. …”

Section: Introductionmentioning

confidence: 99%

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

Wick

Lin

et al. 2017

American Journal of Otolaryngology

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“…ELH has been associated with damage to the organ of Corti and spiral ganglion neurons (SGNs) and is the most well-studied mechanism of hearing loss in XLH [226, 236]. The severity of ELH has also correlated with the severity of hearing loss in Hyp-Duk mice [237].…”

Section: Background and Introductionmentioning

confidence: 99%

FGF23 and its role in X-linked hypophosphatemia-related morbidity

Beck-Nielsen

Mughal

Haffner

et al. 2019

Orphanet J Rare Dis

196

229

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Background X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the Phosphate Regulating Endopeptidase Homolog, X-Linked ( PHEX ) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood. Methods The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH. Results The pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations. Conclusions By describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.

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“…ABRs signals were acquired through intradermal needle electrodes (low impedance (< 5 kΩ), 25G needle diameter) directed to the ear canal of both ears. Ground electrodes were placed in the midline of the animal [ 25 ]. The brainstem signal in response to ipsilateral stimulation (right ear) was amplified 10,000–100,000 times and filtered between 0.3 and 3 kHz.…”

Section: Methodsmentioning

confidence: 99%

The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit

et al. 2016

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Background and ObjectiveThe auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors.MethodsWe used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR).ResultsAuditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes.ConclusionThese findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses.

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A Mouse Model Validates the Utility of Electrocochleography in Verifying Endolymphatic Hydrops

Cited by 12 publications

References 41 publications

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation

FGF23 and its role in X-linked hypophosphatemia-related morbidity

The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit

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