Emerging Research Grants

2019-2020 Emerging Research Grantees Announced

By Christopher Geissler, Ph.D.

ERG_logo-new.png

Hearing Health Foundation (HHF) is proud to announce the recipients of Emerging Research Grants (ERG) for the upcoming year (July 1, 2019 — June 30, 2020). Following a rigorous review process, our Scientific Review Committee and Council of Scientific Trustees, comprised of senior expert scientists and physicians from across the US, have chosen fourteen especially meritorious projects to fund, covering a broad range of hearing and balance science. We are pleased to be able to support the work of these promising researchers and look forward to learning about the advances they will undoubtedly make in the coming year and beyond.

This year’s ERG recipients are:

Dunia Abdul-Aziz, M.D.
Massachusetts Eye and Ear
Project: Targeting epigenetics to restore hair cells

Pierre Apostolides, Ph.D.
Regents of the University of Michigan
Project: Novel mechanisms of cortical neuromodulation

Michael Dent, Ph.D.
University at Buffalo
Project: Noise-induced tinnitus in mice
Generously funded by The Les Paul Foundation

Vijayalakshmi Easwar, Ph.D.
University of Wisconsin Madison
Project: Neural correlates of amplified speech in children with sensorineural hearing loss
Generously funded by The Children’s Hearing Institute

Kristi Hendrickson, Ph.D.
University of Iowa
Project: Neural correlates of semantic structure in children who are hard of hearing
Generously funded by General Grand Chapter Royal Arch Masons

Hao Luo, Ph.D.
Wayne State University
Cochlear electrical stimulation induced tinnitus suppression and related neural activity change in the rat's inferior colliculus
Generously funded by General Grand Chapter Royal Arch Masons

Kristy Lawton, Ph.D.
Washington State University Vancouver
Project: Characterizing noise-induced synaptic loss in the zebrafish lateral line
Generously funded by General Grand Chapter Royal Arch Masons

Anat Lubetzky, P.T., Ph.D.
New York University
Project: A balancing act in hearing and vestibular loss: assessing auditory contribution to multisensory integration for postural control in an immersive virtual environment

David Martinelli, Ph.D.
University of Connecticut Health Center
Project: Creation and validation of a novel genetically-induced animal model for hyperacusis
Generously funded by Hyperacusis Research

Jameson Mattingly, M.D.
The Ohio State University
Project: Differentiating Ménière's disease and vestibular migraine using audiometry and vestibular threshold measurements

Vijaya Prakash Krishnan Muthaiah, P.T., Ph.D.
University at Buffalo
Project: Potential of inhibition of Poly ADP Ribose Polymerase as a therapeutic approach in blast induced cochlear and brain injury.
Generously funded by General Grand Chapter Royal Arch Masons

William “Jason” Riggs, Au.D.
The Ohio State University
Project: electrophysiological characteristics in children with auditory neuropathy spectrum disorder
Generously funded by General Grand Chapter Royal Arch Masons

Gail Seigel, Ph.D.
The Research Foundation of SUNY on behalf of the University at Buffalo
Project: Targeting microglial activation in hyperacusis

Victor Wong, Ph.D.
Burke Medical Research Institute
Project: Targeting tubulin acetylation in spiral ganglion neurons for the treatment of hearing loss

Print Friendly and PDF

In Memoriam: David J. Lim, M.D.

By Nadine Dehgan

Credit: UCLA Head and Neck Surgery

Credit: UCLA Head and Neck Surgery

We recognize with profound sadness the recent passing of David J. Lim, M.D., who was pivotal to the establishment of Hearing Health Foundation (HHF) and remained committed to our research throughout his life.

As a member of our Council of Scientific Trustees (CST)—the governing body of HHF’s Emerging Research Grants (ERG) program—and as a Centurion donor, Lim worked tirelessly to ensure the most promising auditory and vestibular science was championed.

Prior to his appointment to the CST, “Lim contributed to our understanding of the mechanics of hearing through his excellent scanning electron micrographs of the inner ear,” says Elizabeth Keithley, Ph.D, Chair of the Board of HHF. Lim pursued this critical work in 1970 through his first of many ERG grants.

“Lim was also one of the founding members of the Association for Research in Otolaryngology (ARO) and served as the historian of this esteemed scientific organization,” says Judy Dubno, Ph.D., of HHF’s Board of Directors. “Along with HHF, he cared deeply about ARO and will be missed by many.”

Most recently, Lim was a surgeon-scientist and a director of the UCLA Pathogenesis of Ear Diseases Laboratory, where he was considered an authority on temporal bone histopathology, morphology and cell biology of the ear, and the innate immunity of the middle and inner ear.

We, the HHF community, are grateful to have known and to have benefited from Lim’s wisdom, good humor, and kind spirit. HHF will honor his legacy by continuing our mission, knowing we are indebted to his leadership and dedication to advancements in hearing health.

Print Friendly and PDF

Novel Drug-Delivery Method to the Inner Ear

By Gary Polakovic, USC News

Researchers have developed a new approach to be able to repair cells deep inside the ear. The study, conducted by scientists at University of Southern California (USC) and Harvard University, demonstrates a novel way for a future drug to zero in on damaged nerves and cells inside the ear.

Credit: Matthew Pla Savino/USC News

Credit: Matthew Pla Savino/USC News

“What’s new here is we figured out how to deliver a drug into the inner ear so it actually stays put and does what it’s supposed to do, and that’s novel,” says Charles E. McKenna, Ph.D., a corresponding author for the study and chemistry professor at the USC Dornsife College of Letters, Arts, and Sciences.

“Inside this part of the ear, there’s fluid constantly flowing that would sweep dissolved drugs away, but our new approach addresses that problem. This is a first for hearing loss and the ear,” McKenna adds. “It’s also important because it may be adaptable for other drugs that need to be applied within the inner ear.”

The paper was published April 4 in the journal Bioconjugate Chemistry. The authors include lead researcher Judith S. Kempfle, Ph.D., a 2011 and 2012 Emerging Research Grants scientist, as well as Hearing Restoration Project member Albert Edge, Ph.D., both at Harvard Medical School and The Eaton-Peabody Laboratories in Boston.

There are caveats. The research was conducted on animal tissues in a petri dish. It has not yet been tested in living animals or humans. Yet the researchers are hopeful given the similarities of cells and mechanisms involved. McKenna says since the technique works in the laboratory, the findings provide “strong preliminary evidence” it could work in living creatures. They are already planning the next phase involving animals and hearing loss.

The study breaks new ground because researchers developed a novel drug-delivery method. Specifically, it targets the cochlea, a snail-like structure in the inner ear where sensitive cells convey sound to the brain. Hearing loss occurs due to aging or exposure to noise at unsafe levels. Over time, hair-like sensory cells and bundles of neurons that transmit their vibrations break down, as do ribbon-like synapses, which connect the cells.

The researchers designed a molecule combining 7,8-dihydroxyflavone, which mimics a protein critical for development and function of the nervous system, and bisphosphonate, a type of drug that sticks to bones. This pairing delivered the breakthrough solution, the researchers say, as neurons responded to the molecule and regenerated synapses in mouse ear tissue. This led to the repair of the hair cells and neurons, which are essential to hearing.

“We’re not saying it’s a cure for hearing loss,” McKenna says. “It’s a proof of principle for a new approach that’s extremely promising. It’s an important step that offers a lot of hope.” Hearing loss affects two thirds of people over 70 years and 17 percent of all adults in the United States, and it is expected to nearly double in 40 years.

This is adapted from "Hearing Loss Study at USC, Harvard Shows Hope for Millions" on the USC News website. The authors of the April 4, 2018, Bioconjugate Chemistry study, “Bisphosphonate-Linked TrkB Agonist: Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss,” include lead researcher Judith S. Kempfle, as well as Christine Hamadani, Nicholas Koen, Albert S. Edge, and David H. Jung of Harvard Medical School and The Eaton-Peabody Laboratories/Massachusetts Eye and Ear in Boston. Kempfle is also affiliated with the University of Tübingen Medical Center. Corresponding author Charles E. McKenna, as well as Kim Nguyen and Boris A. Kashemirov, are at USC Dornsife.

The research was supported by the American Academy of Otolaryngology–Head and Neck Surgery Herbert Silverstein Otology and Neurotology Research Award, an American Otological Society Research Grant, and a grant from the National Institute of Deafness and other Communicative Disorders (R01 DC007174).

Print Friendly and PDF

HHF Celebrates 60 Years

By Yishane Lee

The legacies of Collette Ramsey Baker and Wesley H. Bradley, M.D., underscore the shared mission of Hearing Health Foundation and the medical community to support and fund groundbreaking scientific research.

60-years.png

Sixty years ago, Collette Ramsey Baker founded Deafness Research Foundation, now known
as Hearing Health Foundation (HHF). After living with a hearing loss for decades, she found relief through fenestration surgery, an early otosclerosis treatment. In gratitude, Ramsey Baker wanted to give back. Her daughter, Collette Wynn, says, “My mother made a promise that, if the operation worked, she would do something to support research to find the causes of deafness and develop better treatments.” HHF was launched in 1958.

Ramsey Baker introduced her surgeon, Julius Lempert, M.D., who pioneered the fenestration surgery, and Walter Petryshyn, M.D., her otolaryngologist (ear, nose, and throat specialist), to finance and industry leaders, and from this talented group came HHF’s first Board of Directors, with Ramsey Baker becoming HHF’s president.

In 2006, this magazine ran a profile of Ramsey Baker featuring the recollections of HHF’s early years from Wesley H. Bradley, M.D., a skilled surgeon who went on to lead what became the National Institute on Deafness and Other Communication Disorders (NIDCD). Bradley passed away in 2012, two years after Ramsey Baker.

In the article, Bradley recounts how HHF’s mission so impressed Lempert that he spoke about the organization to leading otologists. “These individuals quickly saw the advantage of supporting a group that was firmly established to promote otological research,” Bradley said.

One early effort was the creation, in 1960, of a program to encourage people to donate their temporal bones to hearing science upon death. The National Temporal Bone Registry, now
overseen by the NIDCD, has led to countless research breakthroughs.

In 1963, physician support of HHF was formalized with the creation of The Centurions, a group of doctors who covered HHF’s administrative costs so all funds raised went directly to hearing research. Physicians also joined the board and launched the Emerging Research Grants program, which remains HHF’s flagship along with the Hearing Restoration Project research consortium.

Bradley’s three-decade involvement with HHF, including as a founding Centurions member and medical director, was recognized with the Wesley H. Bradley, M.D., Memorial Grant, awarded to a promising ERG scientist in 2014. “I had the idea of honoring Wes’s work,” says Bradley’s wife, Barbara. “The many years he spent working at Deafness Research Foundation, it really was a labor of love. He believed very strongly in its mission.”

Says Elizabeth Keithley, Ph.D., the chair of HHF’s Board of Directors, “Planned giving is a major component of HHF’s success today and into the future. It is with these achievements and many more in mind that we celebrate 60 years and look toward more groundbreaking discoveries in hearing and balance science.”

Yishane Lee is the Editor of Hearing Health magazine, a quarterly publication of HHF. This article originally appeared in the Winter 2018 issue of Hearing Health magazine. Read more about Bradley in “A Family Gift” in the Fall 2014 issue and “A Tribute to Wesley H. Bradley, M.D.” in the Winter 2013 issue.

Print Friendly and PDF

Prenatal Intervention May Be Necessary for Usher Syndrome Treatment

By Carol Stoll

Usher syndrome is a hereditary disorder that affects 1 in 20,000 people worldwide and causes concurrent hearing and vision loss. Though currently there is no cure, scientists have begun to understand the molecular mechanisms of hearing loss in Usher syndrome by identifying the specific mutations in genes associated with auditory hair cell malfunction. Gene-specific targeting has been used to target Usher mutations and restore hearing, but the effectiveness and best timing of the treatment is still being investigated in mouse models. Recent research published in JARO by Emerging Research Grants (ERG) recipient Michelle Hastings, Ph.D., and colleagues shows that early administration of a genetic targeting treatment is critically important for repairing outer hair cells and thus rescuing hearing in those with genetic disorders like Usher syndrome.

prenatal intervention usher syndrome.jpg

Hastings’ research focuses on type 1 Usher, which is the most severe of three subtypes and is associated with six genes. One of these genes, USH1C, contains the instructions to create a protein that localizes to auditory hair cells and helps to maintain their bundle structure and ability to detect sound waves. A mutation in USH1C causes this protein to be cut short and malfunction, and is thus responsible for type 1C Usher in humans. Adding, or “knocking-in,” the mutation to mouse DNA causes symptoms similar to those of human patients with type 1C Usher. These Usher mice exhibit hearing and vision loss as well as deficits in balance, little or no auditory-evoked brainstem response (ABR), and abnormal eye tests called electroretinograms. The hearing loss is linked to defective or missing inner and outer hair cells in the cochlea of the inner ear.

Antisense oligonucleotide (ASO) therapy is a gene-specific targeting therapy previously used by Hastings and her colleagues to rescue hearing in Usher knock-in mice. ASOs are small strands of nucleotides (the building blocks of DNA and RNA) that are specifically synthesized to bind to the disease-causing mutation site of RNA and block it from creating defective RNA and proteins. The ASO therapy targeting the USH1C mutation was administered to the Usher mice a few days after birth. Hearing was rescued and ABR improved, which is indicative of improved inner hair cell function. However, function of the outer hair cells, which surround the inner hair cells and are responsible for amplifying sounds, was not tested.

Hastings’ most recent study, with Jennifer Lentz, Ph.D.’s research group, investigated whether the timing of ASO treatment is important for rescuing outer hair cells in addition to inner hair cells for full hearing rescue. ASO therapy was administered to knock-in Usher mice of varying ages, and then outer hair cell function was tested by measuring distortion product otoacoustic emissions (DPOAEs) in 1-, 3-, and 6-month-old mice. When two tones are presented in the ear canal, outer hair cells that function normally respond by producing amplified sounds known as DPOAEs. In Usher mice, DPOAEs are not detected, which indicates loss of outer hair cell function. ASO treatment was able to recover outer hair cell function measured by DPOAEs when it was administered one day after birth. However, the treatment was not effective if first administered on or after postnatal day five.

The results of this study indicate that there is a developmental window of time when USH1 gene expression is needed to properly develop auditory hair cells, and thus early genetic treatment is essential for hearing rescue of those with Usher syndrome. In humans, hair cell development occurs early in pregnancy, and thus ASO treatment would likely require very early prenatal intervention. ASOs have been approved for clinical use for a number of different diseases in humans, but more animal research is necessary before moving to clinical trials for ASO therapy for Usher syndrome. Hastings has also published research on testing ASO therapy on prenatal mice, and found that injecting ASOs in the amniotic cavity of pregnant mice can in fact access the cochlea. Hastings’ research has improved the scientific community’s understanding of the functions of inner and outer hair cells and brings us closer to developing a cure for Usher syndrome.

Michelle Hastings, Ph.D., was a 2009 and 2011 Emerging Research Grants scientist. For more, see “Rescue of Outer Hair Cells With Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment” in The Journal of the Association for Research in Otolaryngology.

Empower groundbreaking research toward better treatments and cures for Usher syndrome. If you are able, please make a contribution today.

 
 
Print Friendly and PDF

HHF Welcomes New Board Members in April 2017

By Nadine Dehgan

Hearing Health Foundation (HHF) is delighted to welcome Bob Shannon, Ph.D., and Ruth Anne Eatock, Ph.D., to our Board of Directors. Their unwavering commitment toward advancing research to better understand hearing loss and its associated disorders make Drs. Shannon and Eatock perfect additions to our leadership team.

BobShannon.jpeg

Dr. Robert Shannon is a research professor of otolaryngology at the University of Southern California’s Keck School of Medicine with over four decades of experience in researching auditory perception and psychoacoustics. He also serves as an editor and reviewer for several prominent scientific journals and funding agencies and has published more than 100 scientific articles on his research. Most recently Dr. Shannon has been a primary investigator on research studies that advance the technology and effectiveness of the auditory brainstem implant (ABI), an auditory prosthesis for people who have a non-functioning auditory nerve. The ABI is the first device approved by the Food and Drug Administration for prosthetic electrical stimulation of the human brainstem.

“I initially got involved with HHF (then DRF) by joining the Science Review Committee, to ensure the high quality of the research proposals, and later joined the Council of Scientific Trustees,” said Dr. Shannon. “Now I look forward to continued service on the HHF Board of Directors to have an integral role in pushing the Foundation’s research efforts forward.”

Ruth-Anne-Eatock.jpeg

Dr. Ruth Anne Eatock is a professor of neurobiology and the dean of Faculty Affairs for the Biological Sciences Division at the University of Chicago. She trained at McGill, Caltech, the Massachusetts Eye and Ear Infirmary, and MIT, and has held academic positions in otolaryngology and neuroscience departments at University of Rochester, Baylor College of Medicine, and Harvard. She has experience mentoring students, fellows and clinical scientists in sensory processing by the inner ear, reviewing federal and private grant applications, editing and reviewing research papers, and organizing hearing research meetings.  These experiences have given her a broad appreciation of the progress and goals driving our diverse hearing research community.

Dr. Eatock notes: “My first independent grant was a Deafness Research Grant (now known as Emerging Research Grants), so I am well aware of the importance of such seed funding in helping new investigators establish themselves and advance hearing research.”

HHF is excited to have Drs. Bob Shannon and Ruth Anne Eatock as new members of our Board of Directors and we look forward to their contributions toward HHF’s mission. Please join us in giving them both a warm welcome!

Print Friendly and PDF

A Balancing Act Before the Onset of Hearing

By Sonja J. Pyott, Ph.D.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

The development of the auditory system begins in the womb and culminates in a newborn’s ability to hear upon entering the world. While the age at which hearing begins varies across mammals, the sensory structures of the inner ears are active before the onset of hearing. This activity instructs the maturation of the neural connections between the inner ear and brain, an essential component of the proper development of hearing. However, we still know very little about the mechanisms regulating the activity of these sensory structures and their neural connections, specifically during the critical period just before the onset of hearing.

In our paper, “mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea,” soon to be published in an upcoming issue of The Journal of Physiology, we investigate the role of glutamate, a neurotransmitter, in regulating activity of the sensory structures and their connections in the inner ear before the start of hearing.

Neurotransmitters assist in the communication between neurons and are typically classified as either excitatory or inhibitory based on their action. Excitatory action results in stimulation; inhibitory action assists in the calming of the brain. Our research found that although glutamate typically excites activity, it also elicits inhibitory activity. This dual role for glutamate occurs because it activates two distinct classes of glutamate receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs).

Importantly, this dual activation balances excitatory and inhibitory activity of the sensory structures, a balance of which is likely important in the final refinement of the neural connections between the inner ear and brain prior to the onset of hearing.

As part of future research, we will further investigate the role of mGluRs, one the distinct classes of glutamate receptors, in the development of hearing. We will also investigate if mGluRs balance excitatory and inhibitory activity in the adult inner ear, similar to its role prior to the onset of hearing. Insights into these mechanisms may identify new ways to modulate activity and prevent congenital or acquired hearing loss.

Study coauthor Sonja J. Pyott, Ph.D., was a 2007 and 2008 Hearing Health Foundation Emerging Research Grants recipient.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

 
 
Print Friendly and PDF

Cortical Alpha Oscillations Predict Speech Intelligibility

By Andrew Dimitrijevic, Ph.D.

Hearing Health Foundation Emerging Research Grants recipient Andrew Dimitrijevic, Ph.D., and colleagues recently published “Cortical Alpha Oscillations Predict Speech Intelligibility” in the journal Frontiers in Human Neuroscience.

The scientists measured brain activity that originates from the cortex, known as alpha rhythms. Previous research has linked these rhythms to sensory processes involving working memory and attention, two crucial tasks for listening to speech in noise. However, no previous research has studied alpha rhythms directly during a clinical speech in noise perception task. The purpose of this study was to measure alpha rhythms during attentive listening in a commonly used speech-in-noise task, known as digits-in-nose (DiN), to better understand the neural processes associated with speech hearing in noise.

Fourteen typical-hearing young adult subjects performed the DiN test while wearing electrode caps to measure alpha rhythms. All subjects completed the task in active and passive listening conditions. The active condition mimicked attentive listening and asked the subject to repeat the digits heard in varying levels of background noise. In the passive condition, the subjects were instructed to ignore the digits and watch a movie of their choice, with captions and no audio.

Two key findings emerged from this study in regards to the influence of attention, individual variability, and predictability of correct recall.

First, the authors concluded that the active condition produced alpha rhythms, while passive listening yielded no such activity. Selective auditory attention can therefore be indexed through this measurement. This result also illustrates that these alpha rhythms arise from neural processes associated with selective attention, rather than from the physical characteristics of sound. To the authors’ knowledge, these differences between passive and active conditions have not previously been reported.

Secondly, all participants showed similar brain activation that predicted when one was going to make a mistake on the DiN task. Specifically, a greater magnitude in one particular aspect of alpha rhythms was found to correlate with comprehension; a larger magnitude on correct trials was observed relative to incorrect trials. This finding was consistent throughout the study and has great potential for clinical use.

Dimitrijevic and his colleagues’ novel findings propel the field’s understanding of the neural activity related to speech-in-noise tasks. It informs the assessment of clinical populations with speech in noise deficits, such as those with auditory neuropathy spectrum disorder or central auditory processing disorder (CAPD).

Future research will attempt to use this alpha rhythms paradigm in typically developing children and those with CAPD. Ultimately, the scientists hope to develop a clinical tool to better assess listening in a more real-world situation, such as in the presence of background noise, to augment traditional audiological testing.

Andrew Dimitrijevic, Ph.D., is a 2015 Emerging Research Grantee and General Grand Chapter Royal Arch Masons International award recipient. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grants scientists working in the area of central auditory processing disorders (CAPD). We appreciate their ongoing commitment to funding CAPD research.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

 
 
Print Friendly and PDF

Understanding Auditory Processing Disorder

 By Frankie Huang

April 4 is Auditory Processing Disorder Awareness Day and the Hearing Health Foundation is highlighting the effects and challenges associated with living with APD.

Auditory processing disorder (APD), also known as central auditory processing disorder (CAPD), is an auditory deficit affecting how the central nervous system interprets verbal information. Those living with APD show impairments in sound localization, specifically their ability to isolate a sound source in social environments.

Approximately 5% of school-age children have APD. Children with APD often are uncertain about what they hear and have difficulty listening in loud background noises as well as understanding rapid speech. Often distracted, they can struggle to keep up with conversations which impedes their ability to read, spell, and follow oral directions.

Researchers found a correlation between working memory capacity, which is the ability to retain and manipulate information, and speech development. They found that working memory capacity was significantly lower in children with APD and may be the cause of their inability to separate and group incoming information and, in turn, lead to poor speech perception in noisy environments.

Other researchers found that peripheral hearing loss may affect performance in certain APD tests in older adults. Older adults with mild to moderate hearing loss did significantly poorer on tests that require recalling words, identifying high and low tone patterns, and repeating short sentences.

Although APD can be difficult to diagnose, there are telltale signs: poor auditory memory, difficulty identifying sounds, and a delayed response to verbal requests and instructions. APD is sometimes misdiagnosed as ADD/ADHD or dyslexia, so if you suspect you or a loved one may have APD, it is advised that they go through an individual comprehensive assessment with an audiologist for a more accurate diagnosis.

It is important to understand that research is still needed to understand auditory processing disorders, accurate methodologies for diagnosis, and the best interventions for each child or adult. Even though there are available strategies to treat children with APD, researchers are hard at work finding alternative treatments that will improve the lives of those suffering from APD.

Learn about Hearing Health Foundation’s 2016 Emerging Research Grants recipients who are conducting research to improve the lives of those affected by APD. These grantees are General Grand Chapter Royal Arch Masons International award recipients and we are grateful to the Masons for their ongoing support.

Print Friendly and PDF

Presbycusis and the Deterioration of Neural Nets

By Khaleel A. Razak, Ph.D.

This shows cells of the auditory cortex from a young mouse. Cells can be parvalbumin positive (red), or perineuronal positive (green), or have both parvalbumin and perineuronal nets (red surrounded by green). In our paper we show that all three cell types decline with presbycusis. These changes can cause functional deficit in auditory processing.

This shows cells of the auditory cortex from a young mouse. Cells can be parvalbumin positive (red), or perineuronal positive (green), or have both parvalbumin and perineuronal nets (red surrounded by green). In our paper we show that all three cell types decline with presbycusis. These changes can cause functional deficit in auditory processing.

Age-related hearing loss, or presbycusis, affects a third of the population ages 65 and older, and nearly half the population older than age 75. As a result, it is one of the most prevalent hearing disorders, and it also has a high potential for associated tinnitus and deficits in speech recognition.

Presbycusis leads to myriad changes in the central auditory nervous system. One consistent change is the decline in the ability of auditory system neurons to transmit and receive information with precise timing. The timing precision is somewhat like time-stamping a sound, helping to locate and decode it.

As a result, because of changes to the both the inner ear as well as to the central brain regions that process sound, a combination of hearing aids, behavioral training, and pharmacological treatments will be necessary to alleviate presbycusis-related processing deficits. A key step in developing such a combination method is to understand the mechanisms underlying the changes in neurotransmission in the auditory system and to determine how these changes affect sound processing.

Our paper “Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice,” which was published in the journal Frontiers in Aging Neuroscience, focuses on a specialized structure in sensory cortex known as perineuronal nets (PNNs). Made up of large molecules, PNNs are like a mesh helping to stabilize synapse function among neurons. These extracellular matrix components preferentially surround inhibitory neurons in the auditory cortex and are known to be critical to the function and survival of the neurons they surround.

Specifically, a group of neurons known as parvalbumin-expressing (PV+) neurons are surrounded by PNNs. PV+ neurons play a role in network synchronization and providing inhibition that shapes precise temporal encoding. Reduction in the function of PV+ neurons can lead to the processing deficits observed in presbycusis.

Using two different mouse models, we show that PNN expression is reduced with age, and that an age-related decline in PNNs with presbycusis may be related to changes in synapse function, affecting the processing of sound, particularly those that require proper timing. Because PNNs can be pharmacologically regulated, future studies will test if deterioration of PNNs with presbycusis can be delayed or prevented.

Khaleel A. Razak was a 2009 and 2010 Hearing Health Foundation Emerging Research Grants recipient. This study was started with funding by the Hearing Health Foundation in 2009-2010.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

 
 
Print Friendly and PDF