The Role of Tumor Necrosis Factor Alpha (TNFα) in Hearing Loss and Vestibular Schwannomas

Ren, Yin; Stanković, Konstantina M.

doi:10.1007/s40136-018-0186-4

Cited by 25 publications

(23 citation statements)

References 85 publications

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“…TNFRSF1A has been shown to involve in the production of ototoxic reactive oxygen species and has been demonstrated to be specifically upregulated in gentamicin-mediated ototoxicity [ 32 ], suggesting that high expression of TNFRSF1A may have damaging effects on hearing and hair cells [ 32 ]. Besides, TNFRSF1A may cause infiltration of inflammatory cells, which is known to be the main cause of hearing problems [ 33 ]. As for the TNF pathway, genetic knockout of tumor necrosis factor-alpha (TNF-α) or pharmacologically blocking TNF-α expression ameliorated the behavioral phenotype associated with noise-induced tinnitus in mice [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations

Xie

Niu²,

Ping

et al. 2021

BMC Genom Data

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Background Tinnitus is an auditory phantom sensation in the absence of an acoustic stimulus, which affects nearly 15% of the population. Excessive noise exposure is one of the main causes of tinnitus. To now, the knowledge of the genetic determinants of susceptibility to tinnitus remains limited. Results We performed a two-stage genome-wide association study (GWAS) and identified that two single nucleotide polymorphisms (SNPs), rs2846071 located in the intergenic region at 11q13.5 (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.96–3.40, combined P = 4.89 × 10− 6) and rs4149577 located in the intron of TNFRSF1A gene at 12p13.31 (OR = 2.05, 95% CI = 1.89–2.51, combined P = 6.88 × 10− 6), are significantly associated with the susceptibility to noise-induced tinnitus. Furthermore, the expression quantitative trait loci (eQTL) analyses revealed that rs2846071 is significantly correlated with the expression of WNT11 gene, and rs4149577 with the expression of TNFRSF1A gene in multiple brain tissues (all P < 0.05). The newly identified candidate gene WNT11 is involved in Wnt pathway, and TNFRSF1A in the tumor necrosis factor pathway, respectively. Pathway enrichment analyses also showed that these two pathways are closely relevant to tinnitus. Conclusions Our findings highlight two novel loci at 11q13.5 and 12p13.31 conferring susceptibility to noise-induced tinnitus. and suggest that the WNT11 and TNFRSF1A genes might be the candidate causal targets of 11q13.5 and 12p13.31 loci, respectively.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations

Xie

Niu²,

Ping

et al. 2021

BMC Genom Data

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“…Although SNHL is typically caused by aging, overexposure to noise or ototoxic drugs, or genetic mutation, an additional potentially life-threatening cause of SNHL is vestibular schwannoma (VS), a non-malignant tumor arising from Schwann cells of the vestibular portion of the eighth cranial nerve, and extending into the cerebellopontine angle of the brain. A striking 95% of VS patients develop SNHL; additional symptoms can include tinnitus, balance difficulties, and facial paralysis (2). The conventional hypothesis regarding the mechanism underlying VS-induced SNHL is that the tumor compresses the vestibulocochlear nerve, preventing neural signals carrying hearing and balance information from traveling from the inner ear to the brain; however, evidence from multisite, large cohort studies suggests that associations between tumor size and location and SNHL severity are weak (3)(4)(5)(6)(7), and that SNHL may (4,8,9) or may not (8,(10)(11)(12)(13) worsen with tumor growth over time in VS patients.…”

Section: Introductionmentioning

confidence: 99%

Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs

et al. 2020

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Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays a prominent role in the nervous system, mediating a range of physiologic and pathologic functions. In the auditory system, elevated levels of TNF-α have been implicated in several types of sensorineural hearing loss, including sensorineural hearing loss induced by vestibular schwannoma, a potentially fatal intracranial tumor that originates from the eighth cranial nerve; however, the mechanisms underlying the tumor's deleterious effects on hearing are not well-understood. Here, we investigated the effect of acute elevations of TNF-α in the inner ear on cochlear function and morphology by perfusing the cochlea with TNF-α in vivo in guinea pigs. TNF-α perfusion did not significantly change thresholds for compound action potential (CAP) responses, which reflect cochlear nerve activity, or distortion product otoacoustic emissions, which reflect outer hair cell integrity. However, intracochlear TNF-α perfusion reduced CAP amplitudes and increased the number of inner hair cell synapses without paired post-synaptic terminals, suggesting a pattern of synaptic degeneration that resembles that observed in primary cochlear neuropathy. Additionally, etanercept, a TNF-α blocker, protected against TNF-α-induced synaptopathy when administered systemically prior to intracochlear TNF-α perfusion. Findings motivate further investigation into the harmful effects of chronically elevated intracochlear levels of TNF-α, and the potential for etanercept to counter these effects.

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“…PCSK1 is strongly induced in injured nerves and in SCs [ 29 ]. Although TGFα does not have a clear function in PNS cells, its role in VS and immune mediated HL has recently been described [ 30 ]. TGFα has been identified as an ototoxic molecule [ 31 ], thereby its decrease might also be protective.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure

Colciago

Audano

Bonalume

et al. 2021

Cells

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Hearing loss (HL) is the most common sensory disorder in the world population. One common cause of HL is the presence of vestibular schwannoma (VS), a benign tumor of the VIII cranial nerve, arising from Schwann cell (SC) transformation. In the last decade, the increasing incidence of VS has been correlated to electromagnetic field (EMF) exposure, which might be considered a pathogenic cause of VS development and HL. Here, we explore the molecular mechanisms underlying the biologic changes of human SCs and/or their oncogenic transformation following EMF exposure. Through NGS technology and RNA-Seq transcriptomic analysis, we investigated the genomic profile and the differential display of HL-related genes after chronic EMF. We found that chronic EMF exposure modified the cell proliferation, in parallel with intracellular signaling and metabolic pathways changes, mostly related to translation and mitochondrial activities. Importantly, the expression of HL-related genes such as NEFL, TPRN, OTOGL, GJB2, and REST appeared to be deregulated in chronic EMF exposure. In conclusion, we suggest that, at a preclinical stage, EMF exposure might promote the transformation of VS cells and contribute to HL.

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The Role of Tumor Necrosis Factor Alpha (TNFα) in Hearing Loss and Vestibular Schwannomas

Cited by 25 publications

References 85 publications

Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations

Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations

Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs

Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure

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