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Publication : A corticotropin-releasing factor system expressed in the cochlea modulates hearing sensitivity and protects against noise-induced hearing loss.

First Author  Graham CE Year  2010
Journal  Neurobiol Dis Volume  38
Issue  2 Pages  246-58
PubMed ID  20109547 Mgi Jnum  J:159924
Mgi Id  MGI:4453071 Doi  10.1016/j.nbd.2010.01.014
Citation  Graham CE, et al. (2010) A corticotropin-releasing factor system expressed in the cochlea modulates hearing sensitivity and protects against noise-induced hearing loss. Neurobiol Dis 38(2):246-58
abstractText  Noise-induced hearing loss is a highly prevalent occupational injury, yet little is known concerning the signals controlling normal cochlear sensitivity and susceptibility to noise-induced trauma. While the corticotropin-releasing factor (CRF) system is involved in activation of the classic hypothalamic-pituitary-adrenal axis, it is also involved in local physiological responses to stress in many tissues, and is expressed in the inner ear. We demonstrate that mice lacking the CRF receptor CRFR2 exhibit a significantly lower auditory threshold than wild type mice, but this gain of function comes at the price of increased susceptibility to acoustic trauma. We further demonstrate that glutamatergic transmission, purinergic signaling, and activation of Akt (PKB) pathways within the cochlea are misregulated, which may underlie the enhanced sensitivity and trauma susceptibility observed in CRFR2(-/-) mice. Our data suggest that CRFR2 constitutively modulates hearing sensitivity under normal conditions, and thereby provides protection against noise-induced hearing loss.
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