Calcium signaling and genetic rare diseases: An auditory perspective

Richard, E.; Maurice, Tangui; Delprat, Benjamin

doi:10.1016/j.ceca.2023.102702

Cited by 7 publications

(6 citation statements)

References 165 publications

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“…Further investigation of the precise interplay between ICS waves, ATP, and subcompartmental Ca 2+ homeostasis in in mature, hearing cochlea is needed. Nevertheless, the broad involvement of disorders of Ca 2+ homeostasis, the UPR, and mitochondrial stress in genetic (12) and acquired (6,7,14) hearing loss highlight the need for further study to understand the underlying mechanisms in physiologically relevant disease models. In this study, we did not comprehensively evaluate all potential pathways by which noise exposure could induce changes in subcellular-compartment Ca 2+ homeostasis and the associated downstream stress mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Many of these potential pathways – mitochondrial/oxidative stress, and ER stress and the UPR — are activated upon disruption of Ca 2+ homeostasis. In addition to acquired hearing loss, many genetic forms of deafness involve molecules involved in Ca 2+ flow and homeostasis in cochlear cells (12), illustrating the broad-based importance of these pathophysiologic mechanisms. Dysregulation of subcompartmental Ca 2+ homeostasis has been directly implicated in hair-cell death using an aminoglycoside model of ototoxicity in zebrafish hair cells, in which ER Ca 2+ depletion leads to cytosolic Ca 2+ accumulation, mitochondrial Ca 2+ overload, and mitochondrial stress (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

Park,

Li,

Ismail Mohamad

et al. 2024

Preprint

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Exposure to loud noise is a common cause of acquired hearing loss. Disruption of subcellular calcium homeostasis and downstream stress pathways in the endoplasmic reticulum and mitochondria, including the unfolded protein response, have been implicated in the pathophysiology of noise-induced hearing loss. However, studies on the association between calcium homeostasis and stress pathways has been limited due to limited ability to measure calcium dynamics in mature-hearing, noise-exposed mice. We used a genetically encoded calcium indicator mouse model in which GcAMP is expressed specifically in hair cells or supporting cells under control of Myo15Cre or Sox2Cre, respectively. We performed live calcium imaging and UPR gene expression analysis in 8-week-old mice exposed to levels of noise that cause cochlear synaptopathy (98 db SPL) or permanent hearing loss (106 dB SPL). UPR activation occurred immediately after noise exposure and was noise dose-dependent, with the pro-apoptotic pathway upregulated only after 106 dB noise exposure. Spontaneous calcium transients in hair cells and intercellular calcium waves in supporting cells, which are present in neonatal cochleae, were quiescent in mature-hearing cochleae, but re-activated upon noise exposure. 106 dB noise exposure was associated with more persistent and expansive ICS wave activity. These findings demonstrate a strong and dose-dependent association between noise exposure, UPR activation, and changes in calcium homeostasis in hair cells and supporting cells, suggesting that targeting these pathways may be effective to develop treatments for noise-induced hearing loss.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

Park,

Li,

Ismail Mohamad

et al. 2024

Preprint

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“…We recently demonstrated that Ocm -/- OHCs in the prehearing cochlea altered Ca 2+ signaling and delayed maturation of innervation (Yang Yang et al, 2023). Aberrant Ca 2+ in hair cells leads to cochlear pathology (Richard et al, 2023) and there is increased OHC loss in Ocm -/- mice (Climer et al, 2021; Tong et al, 2016). Noise exposure is a common cause of hearing loss, and increases the concentration of cytosolic free Ca 2+ (Fridberger et al, 1998; Zuo et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…In response to sound stimulation, Ca 2+ influx and Ca 2+ -induced Ca 2+ release (CICR) from the endoplasmic reticulum significantly increase intracellular Ca 2+ in cochlear sensory cells. Factors that cause hearing impairment, such as ototoxic drugs, acoustic overstimulation, and aging, are associated with dysregulation of Ca 2+ homeostasis (Fridberger & Ulfendahl, 1996; Kidd Iii & Bao, 2012; Liu & Fechter, 1997; Richard et al, 2023). Two types of specialized sensory cells in the mammalian cochlea, inner hair cells (IHCs) and outer hair cells (OHCs), are involved in the transduction of sound into electrical responses (Dallos, 1992).…”

Section: Introductionmentioning

confidence: 99%

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

Yang,

Jeng,

Murtha

et al. 2024

Preprint

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Tight regulation of Ca2+is crucial for the function of cochlear outer hair cells (OHCs). Dysregulation of Ca2+homeostasis in OHCs is associated with impaired hearing function and contributes to increased vulnerability to environmental insults, such as noise exposure. Ca2+signaling in developing OHCs can be modulated by oncomodulin (OCM), an EF-hand calcium-binding protein. Here, we investigated whether the lack of OCM disrupts the control of intracellular Ca2+in mature OHCs, and influences vulnerability to noise. Using young adult CBA/CaJ mice, we found that OHCs fromOcm-knockout (Ocm-/-) mice exhibited normal biophysical profiles and electromotile responses compared to littermate control OHCs. Moderate noise exposure (95 dB SPL, 2 hrs) caused temporary hearing threshold shifts inOcm+/+andOcm-/-mice but the loss of hearing was permanent forOcm-/-mice. However, whileOcm+/+fully recovered their hearing 2 weeks after noise exposure,Ocm-/-mice showed permanent threshold shifts. Using a genetically encoded Ca2+sensor (GCaMP6s) expressed inOcm+/+andOcm-/-OHCs, we found that chronic noise exposure (95 dB SPL, 9 hrs) increased ATP-induced Ca2+signaling inOcm-/-OHCs compared toOcm+/+OHCs. Chronic noise exposures also caused higher hearing threshold shifts inOcm-/-mice. Prior to noise exposure, P2X2 expression was already upregulated inOcm-/-mice compared toOcm+/+mice. Following chronic noise, P2X2 receptors were upregulated in theOcm+/+cochlea but not in theOcm-/-cochlea, which retains their pre-noise high expression level. We propose that the lack of OCM increases susceptibility to noise. Increased purinergic signaling and dysregulation of cytosolic Ca2+homeostasis could contribute to early onset hearing loss in theOcm-/-mice.

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“…Theme 3, finally, provides an update about the involvement and role of Ca 2+ signals in pathogenesis and pathology. A wide spectrum of diseases is discussed, including breast cancer [25], neurological disorders, such as Alzheimer's disease [26] and Parkinson's disease [27], chemotherapy-induced neuropathy [28], hepatic diseases [29], cardiac diseases [30], polycystic kidney disease [31], pancreatic diseases [32] and auditory diseases [33].…”

mentioning

confidence: 99%

Modalities of cell death, survival and adaptation: The role of the Ca2+-signaling toolkit

Parys,

Bultynck

2023

Cell Calcium

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Calcium signaling and genetic rare diseases: An auditory perspective

Cited by 7 publications

References 165 publications

Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

Modalities of cell death, survival and adaptation: The role of the Ca2+-signaling toolkit

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Calcium signaling and genetic rare diseases: An auditory perspective

Cited by 7 publications

References 165 publications

Noise induces intercellular Ca2+signaling waves and the unfolded protein response in the hearing cochlea

Noise induces intercellular Ca2+signaling waves and the unfolded protein response in the hearing cochlea

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

Modalities of cell death, survival and adaptation: The role of the Ca2+-signaling toolkit

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Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea