Mechanisms of sensorineural cell damage, death and survival in the cochlea

Wong, Ann Chi Yan; Ryan, Allen F.

doi:10.3389/fnagi.2015.00058

Cited by 222 publications

(187 citation statements)

References 182 publications

(210 reference statements)

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“…Impaired hearing (15% of the population) and balance (35%) associated with a risk of falling and severely reduced quality of life (Agrawal et al, 2009) most commonly reflect sensory hair cell (HC) loss (Wong and Ryan, 2015) or auditory synapse degeneration (Kujawa and Liberman, 2009;Spoendlin, 1975). The permanence of hearing loss is likely to be related to the lack of regenerative capacity in the adult cochlea, where HC damage is not followed by differentiation of new cells.…”

Section: Introductionmentioning

confidence: 99%

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

McLean

Eatock

et al. 2016

Development

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Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear -the vestibular and cochlear sensory epithelia and the spiral ganglion -by measuring electrophysiological properties and gene expression. Lgr5 + progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1 + glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin.

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Section: Introductionmentioning

confidence: 99%

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

McLean

Eatock

et al. 2016

Development

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“…This benefit, however, has been gained at a significant cost in the metabolic and mechanical vulnerability of cochlear hair cells and neurons. Loud sound progressively damages type I afferent neurons and OHCs (1). Once damaged beyond repair, these do not regenerate as they do in nonmammalian vertebrates, suggesting that protective mechanisms should exist to preserve cochlear function.…”

mentioning

confidence: 99%

Unmyelinated type II afferent neurons report cochlear damage

Liu

Glowatzki

Fuchs

2015

Proc. Natl. Acad. Sci. U.S.A.

114

102

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In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.type II cochlear afferents | ATP | acoustic trauma | hyperacusis | noxacusis T he mammalian cochlea is the most elaborate of vertebrate auditory organs. The elegantly coiled, mechanically tuned cochlear duct and functional differentiation between inner hair cells (IHCs) and outer hair cells (OHCs), afferent and efferent neuronal connections are among the features that enable the widest acoustic frequency range and most complex vocalizations among vertebrate species. This benefit, however, has been gained at a significant cost in the metabolic and mechanical vulnerability of cochlear hair cells and neurons. Loud sound progressively damages type I afferent neurons and OHCs (1). Once damaged beyond repair, these do not regenerate as they do in nonmammalian vertebrates, suggesting that protective mechanisms should exist to preserve cochlear function. Indeed, middle ear reflexes (2) and efferent inhibition of hair cells (3) can mitigate acoustic trauma to some extent. However, a more effective strategy is simply to avoid or withdraw from sources of trauma, by analogy to limb withdrawal triggered by C-fiber activation in skin.Here, we provide evidence that unmyelinated type II cochlear afferents can report cochlear trauma, a potential trigger for nocifensive behavior. Hyperactivity of type II neurons could contribute as well to the paradoxical hypersensitivity to loud sound that can accompany hearing loss, despite diminished type I afferent function. Hyperacusis is a comorbidity in 80% of tinnitus patients (4) suggesting common pathogenic mechanisms (5). In the most severe cases, hyperacusis is described as debilitating "ear pain" (6). The response to trauma by type II afferents may relate most directly to such ...

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“…There are 15,500 hair cells and 35,000 neurons in each cochlea of a newborn (Wong and Ryan 2015). Both of these types of cells, like most neurons, are perennial cells (Wong and Ryan 2015): "... no epithelial maintenance has been described for the hair cells of the cochlea of mammals, though hair cell addition and repair occur in lower vertebrates... " (Maier et al 2014).…”

Section: Hearing Neuronsmentioning

confidence: 99%

“…Age-related hearing loss, or presbycusis, is well known->50 % in individuals older than 60 (Zhan et al 2010)-and may be aggravated by other factors, such as noise exposure, diabetes, or hypertension (Wong and Ryan 2015). However, even in healthy animals reared in silence, presbycusis is still observed (Sergeyenko et al 2013;Yan et al 2013).…”

Section: Hearing Neuronsmentioning

confidence: 99%

Aging of perennial cells and organ parts according to the programmed aging paradigm

Libertini

Ferrara

2016

AGE

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If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

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Mechanisms of sensorineural cell damage, death and survival in the cochlea

Cited by 222 publications

References 182 publications

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

Unmyelinated type II afferent neurons report cochlear damage

Aging of perennial cells and organ parts according to the programmed aging paradigm

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