The Role of Glia in the Peripheral and Central Auditory System Following Noise Overexposure: Contribution of TNF-a; and IL-1b; to the Pathogenesis of Hearing Loss

Repeated noise exposure induces inflammation and cellular adaptations in the peripheraland central auditory system resulting in pathophysiology of hearing loss. In this study, weanalyzed the mechanisms by which noise-induced inflammatory-related events in thecochlea activate glial-mediated cellular...

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Detalles Bibliográficos
Autores: Fuentes Santamaría, Verónica, Alvarado Romero, Juan Carlos, Melgar Rojas, Pedro, Gabaldón Ull, María Cruz, Miller, Josef M., Juiz Gómez, José Manuel
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/33094
Acceso en línea:https://doi.org/10.3389/fnana.2017.00009
http://journal.frontiersin.org/article/10.3389/fnana.2017.00009/full
https://hdl.handle.net/10578/33094
Access Level:acceso abierto
Palabra clave:Auditory system
Cochlear nucleus
Cytokines
Inflammation
Inner ear
Descripción
Sumario:Repeated noise exposure induces inflammation and cellular adaptations in the peripheraland central auditory system resulting in pathophysiology of hearing loss. In this study, weanalyzed the mechanisms by which noise-induced inflammatory-related events in thecochlea activate glial-mediated cellular responses in the cochlear nucleus (CN), the firstrelay station of the auditory pathway. The auditory function, glial activation, modificationsin gene expression and protein levels of inflammatory mediators and ultrastructuralchanges in glial-neuronal interactions were assessed in rats exposed to broadbandnoise (0.5–32 kHz, 118 dB SPL) for 4 h/day during 4 consecutive days to inducelong-lasting hearing damage. Noise-exposed rats developed a permanent thresholdshift which was associated with hair cell loss and reactive glia. Noise-induced microglialactivation peaked in the cochlea between 1 and 10D post-lesion; their activationin the CN was more prolonged reaching maximum levels at 30D post-exposure.RT-PCR analyses of inflammatory-related genes expression in the cochlea demonstratedsignificant increases in the mRNA expression levels of pro- and anti-inflammatorycytokines, inducible nitric oxide synthase, intercellular adhesion molecule and tissueinhibitor of metalloproteinase-1 at 1 and 10D post-exposure. In noise-exposed cochleae,interleukin-1ß (IL-1ß), and tumor necrosis factor a (TNF-a) were upregulated by reactivemicroglia, fibrocytes, and neurons at all time points examined. In the CN, however,neurons were the sole source of these cytokines. These observations suggest that noiseexposure causes peripheral and central inflammatory reactions in which TNF-a and IL-1ßare implicated in regulating the initiation and progression of noise-induced hearing loss.