Modulation of age-related changes in the auditory system

Summary

Principal Investigator: JAMES WILLOTT
Abstract: [unreadable] DESCRIPTION (provided by applicant): The current project has been investigating a method that dramatically ameliorates age-related hearing loss in several inbred strains of mice that serve as models for presbycusis and other forms of progressive sensorineural hearing loss. The treatment involves an augmented acoustic environment (AAE), an extended period of nontraumatic acoustic stimulation for 12 hours each day. Positive effects of AAE treatment include slowing progressive elevation of auditory brainstem response (ABR) thresholds, diminished loss of outer hair cells and spiral ganglion cells, lessened age-related reduction of volume and neuron loss in the anterior ventral cochlear nucleus (AVCN), increased amplitude of the acoustic startle response, and stronger prepulse inhibition (PPI; indicative of the behavioral salience of sounds). However, in demonstrating these findings, the current project has revealed that the effects of AAE treatment are complicated by several factors including sex, frequency spectrum of the AAE; and age or degree of progressive hearing loss at initiation of AAE treatment. The continuation project addresses these factors, focusing on histopathology of the cochlea and AVCN using D2 and B6 mice. Aim 1 will evaluate an observed sex effect in B6 mice: females between about 6-12 months of age (when fertility and estrogen are declining) exhibk an acceleration in the rate and severity of hearing loss compared to males. Findings stemming from this aim can help us to better understand sexrelated factors that may modulate presbycusis in humans. Aim 2 will elucidate variables respons_le for the positive effects of AAE treatment on cochlear tissue using histological methods. The goal is to gain additional insight into mechanisms associated with AAE effects. Aim 3 will study the role of sex hormones and other variables involved in central AAE effects, including the death in AVCN neurons in AAE-treated male B6 mice and neuron protection observed in females. The findings will have implications with respect to possible effects of the acoustic environment (e.g.,arnplification) on the central auditory system. Aim 4 will evaluate in greater detail the effects of very early initiation of AAE treatment, which has potential clinical implications. The proposed continuation project can help us to better understand progressive sensorineural hearing loss and factors that modulate it, such as sex hormones and age at intervention. The ultimate goal is to develop new approaches for amelioration and treatment ofpresbycusis and other hearing disorders. [unreadable] [unreadable]
Funding Period: 1988-05-01 - 2010-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Effects of exposing DBA/2J mice to a high-frequency augmented acoustic environment on the cochlea and anteroventral cochlear nucleus
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Avenue, PCD4118G, Tampa, FL 33620, USA
    Hear Res 216:138-45. 2006
  2. pmc Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave PCD4118G, Tampa, FL 33620, USA
    Hear Res 221:73-81. 2006
  3. ncbi Factors affecting hearing in mice, rats, and other laboratory animals
    James F Willott
    University of South Florida, Tampa, FL, USA
    J Am Assoc Lab Anim Sci 46:23-7. 2007
  4. pmc Effects of exposing C57BL/6J mice to high- and low-frequency augmented acoustic environments: auditory brainstem response thresholds, cytocochleograms, anterior cochlear nucleus morphology and the role of gonadal hormones
    James F Willott
    Department of Psychology, University of South Florida, Tampa, FL 33620, USA
    Hear Res 235:60-71. 2008
  5. pmc Effects of sex, gonadal hormones, and augmented acoustic environments on sensorineural hearing loss and the central auditory system: insights from research on C57BL/6J mice
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave, PCD4118G, Tampa, FL 33620, USA The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Hear Res 252:89-99. 2009
  6. pmc Effects of a high-frequency augmented acoustic environment on parvalbumin immunolabeling in the anteroventral cochlear nucleus of DBA/2J and C57BL/6J mice
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave PCD4118G, Tampa, FL 33620, USA
    Hear Res 261:36-41. 2010

Detail Information

Publications6

  1. ncbi Effects of exposing DBA/2J mice to a high-frequency augmented acoustic environment on the cochlea and anteroventral cochlear nucleus
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Avenue, PCD4118G, Tampa, FL 33620, USA
    Hear Res 216:138-45. 2006
    ....
  2. pmc Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave PCD4118G, Tampa, FL 33620, USA
    Hear Res 221:73-81. 2006
    ..In an earlier study, the same high-frequency AAE treatment on DBA/2J mice ameliorated hearing loss. The most severe AAE-induced losses occurred in surgically intact females, suggesting a potentiating effect of ovarian hormone(s)...
  3. ncbi Factors affecting hearing in mice, rats, and other laboratory animals
    James F Willott
    University of South Florida, Tampa, FL, USA
    J Am Assoc Lab Anim Sci 46:23-7. 2007
    ..An understanding of genetic and environmental influences on hearing and auditory behavior is important for those who provide, use, and care for laboratory animals...
  4. pmc Effects of exposing C57BL/6J mice to high- and low-frequency augmented acoustic environments: auditory brainstem response thresholds, cytocochleograms, anterior cochlear nucleus morphology and the role of gonadal hormones
    James F Willott
    Department of Psychology, University of South Florida, Tampa, FL 33620, USA
    Hear Res 235:60-71. 2008
    ..In general, LAAE treatment plus male gonadal hormones (intact males) had an ameliorative effect whereas HAAE or LAAE treatment plus ovarian hormones (intact females) had a negative effect on age-related changes in the B6 auditory system...
  5. pmc Effects of sex, gonadal hormones, and augmented acoustic environments on sensorineural hearing loss and the central auditory system: insights from research on C57BL/6J mice
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave, PCD4118G, Tampa, FL 33620, USA The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Hear Res 252:89-99. 2009
    ..Loss of hair cells and AVCN neurons after AAE exposure were more severe in orchidectomized males than in intact males. Ideas, hypotheses, and potential mechanisms concerning the findings are discussed...
  6. pmc Effects of a high-frequency augmented acoustic environment on parvalbumin immunolabeling in the anteroventral cochlear nucleus of DBA/2J and C57BL/6J mice
    James F Willott
    Department of Psychology, University of South Florida, 4202 E Fowler Ave PCD4118G, Tampa, FL 33620, USA
    Hear Res 261:36-41. 2010
    ..The findings suggest that HAAE treatment provides relief from physiological stress caused by deprivation of auditory input from the impaired cochlea...