The spiral ganglion: Connecting the peripheral and central auditory systems

Nayagam, Bryony A; Muniak, Michael A.; Ryugo, David K.

doi:10.1016/j.heares.2011.04.003

Cited by 170 publications

(165 citation statements)

References 174 publications

(244 reference statements)

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“…Conversely, the present study highlights the extensive formation of presynaptic terminals between hESC-derived neurons and hair cells in vitro. The en passant-like nature of the new presynaptic terminals between the stem cell-derived neural processes and the sensory hair cells is intriguing, because of their similarity to the pattern of type II auditory neuron innervation reported in the normal hearing cochlea [50][51][52]. Rather than a single synaptic bouton, which is typical of the type I-inner hair cell synapse, this en passant-like contact may ultimately result in a different physiological function.…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Nayagam

Edge²,

Needham³

et al. 2013

Stem Cells and Development

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In mammals, the sensory hair cells and auditory neurons do not spontaneously regenerate and their loss results in permanent hearing impairment. Stem cell therapy is one emerging strategy that is being investigated to overcome the loss of sensory cells after hearing loss. To successfully replace auditory neurons, stem cell-derived neurons must be electrically active, capable of organized outgrowth of processes, and of making functional connections with appropriate tissues. We have developed an in vitro assay to test these parameters using cocultures of developing cochlear explants together with neural progenitors derived from human embryonic stem cells (hESCs). We found that these neural progenitors are electrically active and extend their neurites toward the sensory hair cells in cochlear explants. Importantly, this neurite extension was found to be significantly greater when neural progenitors were predifferentiated toward a neural crest-like lineage. When grown in coculture with hair cells only (denervated cochlear explants), stem cell-derived processes were capable of locating and growing along the hair cell rows in an en passant-like manner. Many presynaptic terminals (synapsin 1-positive) were observed between hair cells and stem cell-derived processes in vitro. These results suggest that differentiated hESC-derived neural progenitors may be useful for developing therapies directed at auditory nerve replacement, including complementing emerging hair cell regeneration therapies.

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Section: Discussionmentioning

confidence: 99%

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Nayagam

Edge²,

Needham³

et al. 2013

Stem Cells and Development

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“…Indeed, a model of the auditory periphery closely approximates human psychophysical forward masking data when high- and low-SR types are combined (Meddis and O’Mard, 2005). Additionally, because the low-SR fibers are believed to be a major input to the olivocochlear reflex (Liberman, 1988; Nayagam et al, 2011), which serves an “antimasking” role (Kawase et al, 1993), a loss of these fibers should cause deficits in experiments such as forward masking.…”

Section: Discussionmentioning

confidence: 99%

Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

et al. 2017

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In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low-SR fibers results in a faster recovery of wave-V latency as the slow contribution of these fibers is reduced. Results showed that in young audiometrically normal listeners, a larger change in wave-V latency with increasing masker-to-probe interval was related to a greater effect of a preceding masker behaviorally. Further, the amount of wave-V latency change with masker-to-probe interval was positively correlated with the rate of change in forward masking detection thresholds. Although we cannot rule out central contributions, these findings are consistent with the hypothesis that auditory nerve fiber deafferentation occurs in humans and may predict how well individuals can hear in noisy environments.

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“…In an attempt to provide a regenerative therapy for deafness in 2014, Buddy and co-workers successfully forced hBMSCs to express essential genes in the otic lineages 43 . Additionally, BDNF gene-modified MSCs are known to have a protective effect on the spiral ganglion cells 44 . Another example is genetic manipulation for Atoh1 which is a master gene for the differentiation of the hair cells.…”

Section: Recombinant Bmscsmentioning

confidence: 99%

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration

Mahmoudian-Sani

Mehri-Ghahfarrokhi

Hashemzadeh‐Chaleshtori

et al. 2017

The International Tinnitus Journal

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In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy. Mesenchymal stem cells have been reported to invade the damaged area, contribute to the structural reorganization of the damaged cochlea and improve incomplete hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells would be more beneficial than other mesenchymal stem cells.

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The spiral ganglion: Connecting the peripheral and central auditory systems

Cited by 170 publications

References 174 publications

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration

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