Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse

Tang, Xiaolan; Liu, Hanjun; Ding, Bo; Walton, Joseph P.; Frisina, Robert D.; Su, Jiping

doi:10.1016/j.neuroscience.2013.11.058

Cited by 51 publications

(31 citation statements)

References 46 publications

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“…This inbred strain is well established as a "good hearing" standard and "normal aging" model in hearing research. [16][17][18][19][20][21][22][23] Description of use of this protocol in other mammalian models is beyond the scope of this text. The reader should note, however, that the RWN application technique offers several advantages to studying the mammalian inner ear.…”

Section: Discussionmentioning

confidence: 99%

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Stevens

Brown

Ezell

et al. 2015

JoVE

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Investigators have utilized a wide array of animal models and investigative techniques to study the mammalian auditory system. Much of the basic research involving the cochlea and its associated neural pathways entails exposure of model cochleae to a variety of ototoxic agents. This allows investigators to study the effects of targeted damage to cochlear structures, and in some cases, the self-repair or regeneration of those structures. Various techniques exist for delivery of ototoxic agents to the cochlea. When selecting a particular technique, investigators must consider a number of factors, including the induction of inadvertent systemic toxicity, the amount of cochlear damage produced by the surgical procedure itself, the type of lesion desired, animal survivability, and reproducibility/reliability of results. Currently established techniques include parenteral injection, intra-peritoneal injection, trans-tympanic injection, endolymphatic sac injection, and cochleostomy with perilymphatic perfusion. Each of these methods has been successfully utilized and is well described in the literature; yet, each has various shortcomings. Here, we present a technique for topical application of ototoxic agents directly to the round window niche. This technique is non-invasive to inner ear structures, produces rapid onset of reliably targeted lesions, avoids systemic toxicity, and allows for an intra-animal control (the contra-lateral ear). Results stemming from this approach have helped deeper understanding of auditory pathophysiology, cochlear cell degeneration, and regenerative capacity in response to an acute injury. Future investigations may use this method to conduct interventional studies involving gene therapy and stem cell transplantation to combat hearing loss.

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Section: Discussionmentioning

confidence: 99%

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Stevens

Brown

Ezell

et al. 2015

JoVE

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“…A number of rodent studies support the theory that this degradation of temporal precision may be attributed to a significant decrease of inhibitory functions and a consequent loss of balance between excitatory and inhibitory processes in the dorsal cochlear nuclei (Caspary et al 2005; Schatteman et al 2008; Wang et al 2009), inferior colliculi (IC) (Caspary et al 1995), spiral ganglion neurons (Tang et al 2014), and auditory cortices (de Villers-Sidani et al 2010; Hughes et al 2010; Juarez-Salinas et al 2010). …”

Section: Introductionmentioning

confidence: 98%

Effects of Aging on the Encoding of Dynamic and Static Components of Speech

et al. 2015

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Objectives The authors investigated aging effects on the envelope of the frequency following response to dynamic and static components of speech. Older adults frequently experience problems understanding speech, despite having clinically normal hearing. Improving audibility with hearing aids provides variable benefit, as amplification cannot restore the temporal precision degraded by aging. Previous studies have demonstrated age-related delays in subcortical timing specific to the dynamic, transition region of the stimulus. However, it is unknown whether this delay is mainly due to a failure to encode rapid changes in the formant transition because of central temporal processing deficits or as a result of cochlear damage that reduces audibility for the high-frequency components of the speech syllable. To investigate the nature of this delay, the authors compared subcortical responses in younger and older adults with normal hearing to the speech syllables /da/ and /a/, hypothesizing that the delays in peak timing observed in older adults are mainly caused by temporal processing deficits in the central auditory system. Design The frequency following response was recorded to the speech syllables /da/ and /a/ from 15 younger and 15 older adults with normal hearing, normal IQ, and no history of neurological disorders. Both speech syllables were presented binaurally with alternating polarities at 80 dB SPL at a rate of 4.3 Hz through electromagnetically shielded insert earphones. A vertical montage of four Ag–AgCl electrodes (Cz, active, forehead ground, and earlobe references) was used. Results The responses of older adults were significantly delayed with respect to younger adults for the transition and onset regions of the /da/ syllable and for the onset of the /a/ syllable. However, in contrast with the younger adults who had earlier latencies for /da/ than for /a/ (as was expected given the high-frequency energy in the /da/ stop consonant burst), latencies in older adults were not significantly different between the responses to /da/ and /a/. An unexpected finding was noted in the amplitude and phase dissimilarities between the two groups in the later part of the steady-state region, rather than in the transition region. This amplitude reduction may indicate prolonged neural recovery or response decay associated with a loss of auditory nerve fibers. Conclusions These results suggest that older adults’ peak timing delays may arise from decreased synchronization to the onset of the stimulus due to reduced audibility, though the possible role of impaired central auditory processing cannot be ruled out. Conversely, a deterioration in temporal processing mechanisms in the auditory nerve, brainstem, or midbrain may be a factor in the sudden loss of synchronization in the later part of the steady-state response in older adults.

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“…In addition, activin was found to compensate for declined NMDA receptor conditions [Kurisaki et al, 2008]. It is therefore tempting to speculate that activin itself bears as yet undiscovered influences in the cochlear nervous system, playing a role in presbycusis [Tang et al, 2014], possibly in tinnitus and perhaps in sensorineural hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Activin Signaling Disruption in the Cochlea Does Not Influence Hearing in Adult Mice

Horvath¹,

Bodmer

Radojević

et al. 2014

Audiol Neurotol

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Activin, a member of the TGF-F superfamily, was found to play an important role in the development, repair and apoptosis of different tissues and organs. Accordingly, activin signaling is involved in the development of the cochlea. Activin binds to its receptor ActRII, then dimerizes with ActRI and induces a signaling pathway resulting in gene expression. A study reported a case of fibrodysplasia ossificans progressiva with an unusual mutation in the ActRI gene leading to sensorineural hearing loss. This draws attention to the role of activin and its receptors in the developed cochlea. To date, only the expression of ActRII is known in the adult mammalian cochlea. In this study, we present for the first time the presence of activin A and ActRIB in the adult cochlea. Transgenic mice with postnatal dominant-negative ActRIB expression causing disruption of activin signaling in vivo were used for assessing cochlear morphology and hearing ability through the auditory brainstem response (ABR) threshold. Nonfunctioning ActRIB did not affect the ABR thresholds and did not alter the microscopic anatomy of the cochlea. We conclude, therefore, that activin signaling is not necessary for hearing in adult mice under physiological conditions but may be important during and after damaging events in the inner ear. i 2014 S. Karger AG, Basel

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Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse

Cited by 51 publications

References 46 publications

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Effects of Aging on the Encoding of Dynamic and Static Components of Speech

Activin Signaling Disruption in the Cochlea Does Not Influence Hearing in Adult Mice

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