Cholesterol Homeostasis in Auditory Function

Summary

Principal Investigator: MICHELLE LYNN SEYMOUR
Abstract: DESCRIPTION (provided by applicant): Hearing loss is the most common sensory impairment, affecting 1 to 6 per 1000 newborns, nearly 10% of the adult population and 50% of those over age 75. Presbycusis is the most common cause of hearing loss, involves age-related degeneration of the inner ear, and results in a sensorineural hearing loss beginning at the high frequencies and progressing to the middle and low frequencies. Although animal models and human studies support a link between hypercholesterolemia and sensorineural hearing loss that implicates pathologies affecting the cochlea, auditory nerve and/or central auditory pathways, fundamental information is lacking to explain this relationship. Mechanistic evidence and knowledge of the relative quantities, biochemical states and species of lipids in the cochlea and how cell functions are affected by altered cholesterol homeostasis are also absent. We hypothesize that cholesterol homeostasis is essential for hearing function and maintenance, and that changes in cholesterol lead to decreased cochlear and hearing function. I propose to determine how acute and chronic elevation of systemic cholesterol affect cochlear cholesterol homeostasis and hearing function and to elucidate the underlying pathologies and mechanisms by which severe hypercholesterolemia affects the adult and aging cochlea. These studies will define the extent and temporal nature of the relationships between alterations in serum cholesterol, cholesterol homeostasis in the cochlea and auditory function, as well as develop an understanding of the pathology underlying this relationship. Hearing loss is becoming an increasing challenge to public health as lifespan increases and the general population ages. As such, the rising prevalence of obesity and hypercholesterolemia demands a better understanding how cholesterol homeostasis influences cochlear cellular activities and hearing function. The outcomes from this proposal will form a crucial basis to develop new therapeutic approaches to preserve auditory function and/or treat age-related hearing loss.
Funding Period: 2012-09-01 - 2015-08-31
more information: NIH RePORT

Top Publications

  1. pmc Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice
    Xiaojun Ma
    US Department of Agriculture Agricultural Research Service Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Physiol Endocrinol Metab 303:E422-31. 2012
  2. pmc An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions
    Bum Jun Kim
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 8:e57460. 2013
  3. pmc Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti
    Tiantian Cai
    Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 33:10110-22. 2013

Detail Information

Publications3

  1. pmc Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice
    Xiaojun Ma
    US Department of Agriculture Agricultural Research Service Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Physiol Endocrinol Metab 303:E422-31. 2012
    ..The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway...
  2. pmc An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions
    Bum Jun Kim
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 8:e57460. 2013
    ....
  3. pmc Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti
    Tiantian Cai
    Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 33:10110-22. 2013
    ..Together our data suggest that Atoh1 regulates multiple aspects of hair cell development and function...

Research Grants30

  1. Role of connexins in cochlear functions
    Xi Lin; Fiscal Year: 2013
    ..In this project we will investigate functional roles of Cx26 in the normal maturation of the hearing organ (the organ of Corti) and novel means to rescue hearing of Cx30 null mutant mice by a genetic approach. ..
  2. Thrombus Formation and Antithrombotic Intervention
    John H Griffin; Fiscal Year: 2013
    ..New knowledge will contribute to improving prevention, diagnosis and treatment of relevant diseases related to thrombosis. ..
  3. Identifying the Atoh1 targetome in hair cells with deep sequencing
    Andrew K Groves; Fiscal Year: 2013
    ..We now propose to apply these same methods to identify the Atoh1 targetome in hair cells. ..
  4. Myosin 15:Genetics, Pathology and Therapeutic Potential
    Sally A Camper; Fiscal Year: 2013
    ..This team will enable us to exploit the animal models fully to understand the mechanisms of inner ear disease and has the potential to identify novel genes essential for normal hearing. ..
  5. Reconstruction of the ascending neural circuit from the spiral ganglion
    Zhengqing Hu; Fiscal Year: 2013
    ..These findings may be used to improve the efficacy of cochlear implants, which rely on SGN stimulation to communicate auditory information to the brain. 1 ..
  6. Optopathology by Light Microscopy and Molecular Techniques
    Michael J McKenna; Fiscal Year: 2013
    ....
  7. The role of MafB in auditory synapse development
    Wei Ming Yu; Fiscal Year: 2013
    ..Together, these studies will provide the opportunity to elucidate the molecular mechanisms of auditory synaptogenesis and may identify novel deafness susceptibility genes. ..
  8. Understanding thyroid hormone regulation of neurogenesis in the cochlea
    Mirna Mustapha; Fiscal Year: 2013
    ..Basic information about the molecular genetics and hormonal regulation of cochlear innervation will emerge from these studies, potentially informing efforts at improving innervation of regenerating hair cells. ..
  9. Thiamine Deficiency and Acquired Auditory Neuropathy
    M Charles Liberman; Fiscal Year: 2013
    ....
  10. Cochlear trafficking and hair cell uptake of aminoglycosides
    PETER STEPHEN STEYGER; Fiscal Year: 2013
    ....
  11. Patterning the tonotopic axis of the cochlea
    Benjamin R Thiede; Fiscal Year: 2013
    ..Finally, I aim to modulate candidate signaling pathways in vitro and in ovo to determine whether such manipulations disrupt normal patterning of HC phenotypes along the longitudinal axis of the cochlea. ..
  12. Regulation of outer hair cell electromotility and noise-induced hearing loss
    Gregory I Frolenkov; Fiscal Year: 2013
    ..The experimental results should help scientists develop treatments for the noise-induced hearing loss, which is one of the most common causes of deafness and hearing impairment. ..
  13. Cytoskeletal dynamics in stereocilia maintenance
    Benjamin J Perrin; Fiscal Year: 2013
    ....
  14. Perceptual and central auditory consequences of noise-induced hearing loss
    Amanda M Lauer; Fiscal Year: 2013
    ..These studies will provide important information for understanding complex hearing deficits and may have implications for improving treatment of hearing loss and for noise trauma prevention guidelines. ..
  15. IDENTIFICATION OF ACOUSTICO-LATERALIS TRANSMITTERS
    Dennis G Drescher; Fiscal Year: 2013
    ....
  16. Potassium Homeostasis in the Inner Ear
    Ebenezer N Yamoah; Fiscal Year: 2013
    ..abstract_text> ..
  17. IN VITRO STUDIES OF THE COCHLEAR NUCLEUS
    Donata Oertel; Fiscal Year: 2013
    ..These experiments will elucidate how pathways through the brain stem carry information necessary for understanding speech. ..
  18. Cochlear Implants in Reinnervated Ears
    Yehoash Raphael; Fiscal Year: 2013
    ..These experiments will set the groundwork for clinical methods to induce nerve regeneration that could enhance the outcome of cochlear implant procedures in patients with severe or profound sensorineural hearing loss. ..
  19. Fibrovascular coupling in the cochlea and pericyte recruitment after noise
    Xiao Rui Shi; Fiscal Year: 2013
    ....
  20. Diagnosing outer hair cell health along the cochlear partition
    Mark E Chertoff; Fiscal Year: 2013
    ..abstract_text> ..
  21. The Role of Glutathione Reductase in Age-related Hearing Loss
    Shinichi Someya; Fiscal Year: 2013
    ..This proposed study will advance understanding of the fundamental molecular mechanisms underlying the anti-aging action of CR in the auditory system in mammals. ..