Cell Death and Cochlear Protection

Green, Steven H.; Altschuler, Richard A.; Miller, Josef M.

doi:10.1007/978-0-387-72561-1_10

Cited by 17 publications

(14 citation statements)

References 248 publications

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“…In support of this, Postigo et al (Postigo et al, 2002) have identified biochemical differences between TrkB and TrkC that could account for functional differences such as those discussed here. BDNF and NT-3 have been proposed as potential therapeutics to prevent SGN degeneration in deaf individuals (Green et al, 2008). These data indicating that they are in fact not equivalent must be considered when designing such therapies.…”

Section: Discussionmentioning

confidence: 99%

Functional Role of Neurotrophin-3 in Synapse Regeneration by Spiral Ganglion Neurons on Inner Hair Cells after Excitotoxic TraumaIn Vitro

Wang¹,

Green²

2011

J. Neurosci.

134

165

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Spiral ganglion neurons (SGNs) are postsynaptic to hair cells and project to the brainstem. The inner hair cell (IHC) to SGN synapse is susceptible to glutamate excitotoxicity and to acoustic trauma, with potentially adverse consequences to long-term SGN survival. We used a cochlear explant culture from P6 rat pups consisting of a portion of organ of Corti maintained intact with the corresponding portion of spiral ganglion to investigate excitotoxic damage to IHC-SGN synapses in vitro. The normal innervation pattern is preserved in vitro. Brief treatment with NMDA and kainate results in loss of IHC–SGN synapses and degeneration of the distal type 1 SGN peripheral axons, mimicking damage to SGN peripheral axons caused by excitotoxicity or noise in vivo. The number of IHC presynaptic ribbons is not significantly altered. Reinnervation of IHCs occurs and regenerating axons remain restricted to the IHC row. However, the number of postsynaptic densities (PSDs) does not fully recover and not all axons regrow to the IHCs. Addition of either NT-3 or BDNF increases axon growth and synaptogenesis. Selective blockade of endogenous NT-3 signaling with TrkC-IgG reduced regeneration of axons and PSDs, but TrkB-IgG, which blocks BDNF, has no such effect, indicating that endogenous NT-3 is necessary for SGN axon growth and synaptogenesis. Remarkably, TrkC-IgG reduced axon growth and synaptogenesis even in the presence of BDNF, indicating that endogenous NT-3 has a distinctive role, not mimicked by BDNF, in promoting SGN axon growth in the organ of Corti and synaptogenesis on IHCs.

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Section: Discussionmentioning

confidence: 99%

Functional Role of Neurotrophin-3 in Synapse Regeneration by Spiral Ganglion Neurons on Inner Hair Cells after Excitotoxic TraumaIn Vitro

Wang¹,

Green²

2011

J. Neurosci.

134

165

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“…For example, some cell types lack “competence to die” even after cytochrome c release because of low expression of pro-apoptotic regulators (Deshmukh and Johnson 1998) while other cells might quickly progress to their demise. Likewise, apoptosis is not an inevitable outcome of a presumed death signal such as JNK activation (Liu et al, 1996) when other anti-apoptotic or homeostatic pathways intervene (for an account of cell death and survival relevant to the inner ear, see Green et al 2008). This is the context in which we must view the early appearance of apoptotic signals in cell populations that do not die until much later or not at all as illustrated by calpain expression in surviving pillar cells.…”

Section: Discussionmentioning

confidence: 99%

Activation of cell death pathways in the inner ear of the aging CBA/J mouse

2009

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We have previously demonstrated that oxidative stress increases in the inner ear of aging CBA/J mice and might contribute to the loss of function of the sensory system. We now investigate the activation of cell death pathways in the cochlea of these animals. Middle-aged (12 months) and old (18-26 months) mice with hearing deficits displayed outer hair cell nuclei with apoptotic and, to a lesser extent, necrotic features. Both intrinsic and extrinsic cell death pathways were activated by translocation or post-translational modification of proteins in the aging cochlea as compared to young (3 months) animals. Cytosolic cytochrome C increased, formed a complex with, and activated caspase 9. Endonuclease G translocated to the nuclei of aging outer hair cells suggesting its function as an apoptotic DNase. The cleaved (and hence active) forms of calpain I and calpain II increased while active cathepsin D was transiently elevated in middle-aged but not old animals. Finally, increases in the phosphorylation of p38 MAPK and JNK implicated the additional involvement of the MAPK pathway. The results suggest that multiple cell death pathways, all potentially linked to oxidative stress, are activated in hair cells of the auditory organ in aging mice.

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“…Another line of protection has successfully utilized neurotrophins, though the efficacy of neurotrophic factors varies with the individual compounds and the dose administered [58,59,60,61,62]. Direct injection of glial cell line-derived neurotrophic factor (GDNF) into the guinea pig cochlea provided protection in a dose-dependent manner, although high doses of GDNF actually increased susceptibility to noise [58].…”

Section: Noise-induced Hearing Loss (Nihl) - Backgroundmentioning

confidence: 99%

Emerging treatments for noise-induced hearing loss

Oishi¹,

Schacht²

2011

Expert Opinion on Emerging Drugs

157

118

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Introduction Approximately 5% of the population worldwide suffer from industrial, military, or recreational noise-induced hearing loss (NIHL) at great economic cost and detriment to the quality of life of affected individuals. This review discusses pharmacological strategies to attenuate NIHL that have been developed in animal models and that are now beginning to be tested in field trials. Areas covered The review describes the epidemiology, pathology and pathophysiology of NIHL in experimental animals and human. The underlying molecular mechanisms of damage are then discussed as a basis for therapeutic approaches to ameliorate the loss of auditory function. Finally, studies in military, industrial, and recreational settings are evaluated. Literature was searched employing the terms “noise-induced hearing loss” and “noise trauma”. Expert opinion NIHL, in principle, can be prevented. With the current pace of development, oral drugs to protect against NIHL should be available within the next 5 to 10 years. Positive results from ongoing trials combined with additional laboratory tests might accelerate the time from the bench to clinical treatment.

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Cell Death and Cochlear Protection

Cited by 17 publications

References 248 publications

Functional Role of Neurotrophin-3 in Synapse Regeneration by Spiral Ganglion Neurons on Inner Hair Cells after Excitotoxic TraumaIn Vitro

Functional Role of Neurotrophin-3 in Synapse Regeneration by Spiral Ganglion Neurons on Inner Hair Cells after Excitotoxic TraumaIn Vitro

Activation of cell death pathways in the inner ear of the aging CBA/J mouse

Emerging treatments for noise-induced hearing loss

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