Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: Correlations with inner hair cell loss and outer hair cell loss

Kraus, Kari Suzanne; Ding, Dalian; Jiang, Haiyan; Kermany, Mohammad Habiby; Mitra, Sunayana; Salvi, Richard

doi:10.1016/j.heares.2013.05.002

Cited by 6 publications

(5 citation statements)

References 71 publications

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“…Here, following a noise insult, we found no clear alterations in Ntnt1 (data not shown), but Gap43 expression was differently regulated in both genotypes by the noise challenge. These data are in agreement with the reported increased expression of this synaptic plasticity marker in the presence of IGF-1 [ 56 ] and also with its upregulation in the auditory brainstem following cochlear damage and HC loss [ 57 ].…”

Section: Discussionsupporting

confidence: 91%

IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Celaya

Rosa

Bermúdez-Muñoz

et al. 2021

Cells

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Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

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Section: Discussionsupporting

confidence: 91%

IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Celaya

Rosa

Bermúdez-Muñoz

et al. 2021

Cells

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“…These neuroplastic changes are triggered by the loss of neural activity flowing from the auditory nerve into the DCN and VCN, the first relay stations in the ascending pathway. In cases of severe hearing loss exemplified by our 126 dB SPL exposure, extensive degeneration of auditory nerve fibers occurs in the cochlear nucleus (Morest et al, 1998, Hildebrandt et al, 2011, Kraus et al, 2013, Baizer et al, 2015. Auditory nerve fiber degeneration can continue for many months and is accompanied by reactive axonal outgrowth, synaptogenesis and microglia activation, structural substrates for auditory neuroplasticity (Benson et al, 1997, Hildebrandt et al, 2011, Kraus et al, 2011, Baizer et al, 2015.…”

Section: Discussionmentioning

confidence: 99%

Synaptic Reorganization Response in the Cochlear Nucleus Following Intense Noise Exposure

Manohar¹,

Pv²,

Salvi³

et al. 2019

Neuroscience

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The cochlear nucleus, located in the brainstem, receives its afferent auditory input exclusively from the auditory nerve fibers of the ipsilateral cochlea. Noise-induced neurodegenerative changes occurring in the auditory nerve stimulate a cascade of neuroplastic changes in the cochlear nucleus resulting in major changes in synaptic structure and function. To identify some of the key molecular mechanisms mediating this synaptic reorganization, we unilaterally exposed rats to a high intensity noise that caused significant hearing loss and then measured the resulting changes in a synaptic plasticity gene array targeting neurogenesis and synaptic reorganization. We compared the gene expression patterns in the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN) on the noise-exposed side versus the unexposed side using a PCR gene array at 2 d (early) and 28 d (late) post-exposure. We discovered a number of differentially-expressed genes, particularly those related to synaptogenesis and regeneration. Significant gene expression changes occurred more frequently in the VCN than the DCN and more changes were seen at 28 d versus 2 d post-exposure. We confirmed the PCR findings by in situ hybridization for Brain-derived neurotrophic factor (Bdnf), Homer-1, as well as the glutamate NMDA receptor Grin1, all involved in neurogenesis and plasticity. These results suggest that Bdnf, Homer-1 and Grin1 play important roles in synaptic remodeling and homeostasis in the cochlear nucleus following severe noiseinduced afferent degeneration.

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“…High intensity noise causes degeneration of auditory nerve fibers and extensive synaptic modifications in the CN (Baizer et al, 2015; Kim et al, 2004; Kraus et al, 2013; Lin et al, 2011; Morest and Bohne, 1983) including modification of synaptic inputs from non-auditory areas associated with multisensory integration (Dehmel et al, 2012; Levine, 1999; Zhou et al, 2007). Despite the loss of auditory input, noise-induced hearing loss leads to a significant increase in spontaneous activity in the CN.…”

Section: Discussionmentioning

confidence: 99%

“…Acoustic overstimulation and ototoxic drugs lead to the degeneration of auditory nerve fibers and synaptic losses in the CN (Kim et al, 2004; Kraus et al, 2013; Morest and Bohne, 1983). Auditory nerve fiber degeneration is strongly correlated with chronic tinnitus (Bauer et al, 2007a) and hyperacusis (Hickox and Liberman, 2014), suggesting that auditory nerve fiber degeneration may trigger spontaneous hyperactivity in the CN.…”

Section: Introductionmentioning

confidence: 99%

Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling

Manohar

Dahar

Adler

et al. 2016

Molecular and Cellular Neuroscience

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Severe noise-induced damage to the inner ear leads to auditory nerve fiber degeneration thereby reducing the neural input to the cochlear nucleus (CN). Paradoxically, this leads to a significant increase in spontaneous activity in the CN which has been linked to tinnitus, hyperacusis and ear pain. The biological mechanisms that lead to an increased spontaneous activity are largely unknown, but could arise from changes in glutamatergic or GABAergic neurotransmission or neuroinflammation. To test this hypothesis, we unilaterally exposed rats for 2 h to a 126 dB SPL narrow band noise centered at 12 kHz. Hearing loss measured by auditory brainstem responses exceeded 55 dB from 6 to 32 kHz. The mRNA from the exposed CN was harvested at 14 or 28 days post-exposure and qRT-PCR analysis was performed on 168 genes involved in neural inflammation, neuropathic pain and glutamatergic or GABAergic neurotransmission. Expression levels of mRNA of Slc17a6 and Gabrg3, involved in excitation and inhibition respectively, were significantly increased at 28 days post-exposure, suggesting a possible role in the CN spontaneous hyperactivity associated with tinnitus and hyperacusis. In the pain and inflammatory array, noise exposure up-regulated mRNA expression levels of four pain/inflammatory genes, Tlr2, Oprd1, Kcnq3 and Ntrk1 and decreased mRNA expression levels of two more genes, Ccl12 and Il1β. Pain/inflammatory gene expression changes via Ntrk1 signaling may induce sterile inflammation, neuropathic pain, microglial activation and migration of nerve fibers from the trigeminal nerve and cuneate and vestibular nuclei into the CN. These changes could contribute to somatic tinnitus, hyperacusis and otalgia.

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Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: Correlations with inner hair cell loss and outer hair cell loss

Cited by 6 publications

References 71 publications

IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Synaptic Reorganization Response in the Cochlear Nucleus Following Intense Noise Exposure

Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling

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