title: Heat shock factor 1-deficient mice exhibit decreased recovery of hearing following noise overstimulation.
abstract: Heat shock proteins (Hsps) can enhance cell survival in response to stress. Heat shock factor 1 (Hsf1) is the major transcription factor that regulates stress-inducible Hsp expression. We previously demonstrated the presence of Hsf1 in the rodent cochlea and also demonstrated that a heat shock known to precondition the cochlea against noise trauma results in Hsf1 activation in the rodent cochlea. In the present study, we used an Hsf1-deficient (Hsf1-/- mouse model to determine whether eliminating the Hsf1-dependent stress pathway would influence hearing loss and/or recovery from a moderate-intensity noise. Hsf1-/- mice and their normal littermates (Hsf1+/+) were exposed to a 98-dB, broadband (2-20 kHz) noise for 2 hr, and auditory brainstem response thresholds were measured at three frequencies (4, 12, and 20 kHz) 3 hr, 3 days, and 2 weeks after noise. Hsf1-/- mice had greater hearing loss than Hsf1+/+ mice, with significant differences in recovery observed at all frequencies tested by 2 weeks after noise. Increased outer hair cell loss was also observed in Hsf1-/- mice following noise. These studies provide evidence for the importance of Hsf1 in cochlear protection, recovery, and/or repair following noise overstimulation.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology/Head Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
authors.forename: Damon A
authors.initials: DA
authors.lastname: Fairfield
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Lomax
authors.forename: Gary A
authors.initials: GA
authors.lastname: Dootz
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Galecki
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Benjamin
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Altschuler
mesh_terms: D000818:Animals; D003051:Cochlea / Q000473:pathology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018072:Hair Cells, Auditory, Outer / Q000473:pathology / Q000502:physiology; D006309:Hearing; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000503:physiopathology*; D000076249:Heat Shock Transcription Factors; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009622:Noise / Q000009:adverse effects; D020127:Recovery of Function; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors