Hearing Beyond the Hair Cell

By Yehoash Raphael, Ph.D.

Recently, it became clear that loud signals can also damage the connecting interface between the hair cell and the auditory nerve. This interface is the synapse. When the synapse is disrupted, hearing is impaired even without the loss of hair cells, leading to a condition called synaptopathy.

Experiments using transgenic mice showed that elevating levels of a specific molecule called NT3 in the area of the synapse can heal synaptopathy caused by exposure to loud noise. Since transgenic technology is a research tool not applicable for clinical use on humans, it is now necessary to design methods for elevating NT3 in human ears, leading to repair of synaptopathy. This is an important task, because if left untreated, synaptopathy progresses to include nerve cell death and permanent hearing deficits.

One potential way to increase NT3 concentration in the cochlea is by the use of gene transfer technology, which is based on infecting cochlear cells with viruses that are engineered to secrete NT3 and not cause infections. A potential risk of this method is that the site of NT3 is not restricted to the area of the synapses affected by the synaptopathy; NT3 can influence other types of cells.

In my lab at the University of Michigan, we tested the outcome of injecting such viruses on the structure and function of normal (intact) ears. We determined that the procedure resulted in the deterioration of hearing thresholds, and the auditory nerve and its connectivity to the hair cells were also negatively affected.

This negative outcome indicates that treatment of synaptopathy should be based on a more specific way to provide NT3 in an area restricted to the synaptic region. My work with the Hearing Restoration Project is dedicated to optimization of gene transfer technology in the cochlea, and may assist in finding more detailed methods for NT3 gene transfer that better target affected cells.

More information on Dr. Raphael’s research can be found in his report, “Viral-mediated Ntf3 overexpression disrupts innervation and hearing in nondeafened guinea pig cochleae,” published in the journal Molecular Therapy—Methods & Clinical Development on August 3, 2016.

Yehoash Raphael, Ph.D., is the The R. Jamison and Betty Williams Professor at the Kresge Hearing Research Institute, in the Department of Otolaryngology–Head and Neck Surgery at the University of Michigan.

New Player Identified in Hair Cell Development

By Betty Zou, Sunnybrook Research Institute

Sensory hair cells (red) and supporting cells (green) are intricately organized in the developed cochlea. Supporting cells have high levels of the Kremen1 protein, which is stained with a green fluorescent marker here. [Image courtesy of Dr. Alain Dabdoub]

There are roughly 37.2 trillion cells in the human body, each of which can be categorized into one of about 200 different types. What’s remarkable about this immense number and diversity of cells is that they all came from a microscopic cluster that comprises the embryo. Many of these early progenitor cells start out the same, but they receive different programming instructions along the way that enable them to replicate and differentiate to form various tissues and organs.

Signalling pathways are cellular communication systems that govern whether a cell keeps dividing or stops, where it goes and, ultimately, what it becomes. One such pathway is Wnt (pronounced “wint”) signalling, a group of signal transmission networks that play a critical role in embryonic development. Dr. Alain Dabdoub, a scientist in Biological Sciences at Sunnybrook Research Institute, is studying how Wnt signalling affects inner ear development and hearing. A new study by his team has shown for the first time that Kremen1, a poorly understood member of the Wnt network, plays a direct role in the formation of the cochlea, a spiral-shaped auditory sensory organ in the inner ear.

“We know that initially at the very early stages [of development], Wnt signalling pushes cells to proliferate,” says Dabdoub. “Then division stops and cell differentiation occurs. We’re trying to find out what promotes this high level of Wnt and also what decreases it.”

Kremen1 is a protein that sits on the cell surface where it receives and transmits signals to the cellular machinery inside. Previous studies have shown that it blocks Wnt signalling, so Dabdoub and his team decided to investigate whether Kremen1 is involved in cell differentiation in the cochlea.

The researchers found that at an early embryonic stage Kremen1 was present in the precursor cells that give rise to hair cells and supporting cells. Shortly thereafter, Kremen1 was only found in the supporting cells that surround hair cells. When the researchers forced the precursor cells to overproduce Kremen1, fewer of them went on to become hair cells and more became supporting cells. In contrast, knocking down levels of Kremen1 resulted in more hair cells. The results were published in August 2016 in the journal Scientific Reports.

The cochlea contains tens of thousands of hair cells, which have hair bundles on their surface to detect and amplify sound. In mammals, when these cells are damaged or destroyed, they are not replaced and hearing loss results. Supporting cells, on the other hand, remain abundant during an individual’s lifetime and do not appear to be affected by the insults that batter hair cells.

Dabdoub’s research seeks to understand how the cochlea and hair cells form, as well as how these sensory cells can be replenished to restore hearing. “If you think about regeneration, where are the cells that you’re going to regenerate coming from?” he says.

The survival of supporting cells makes them excellent candidates from which to regrow hair cells, but they must first replicate to ensure there are enough to maintain a stable number of supporting cells and form new hair cells. Dabdoub thinks that exploiting the proliferation-enhancing properties of Wnt signalling will help achieve this. His finding that Kremen1 plays an important role in cell fate decisions in the cochlea will be critical to future efforts to regenerate hair cells. “This is a molecule that we should keep an eye on as we work towards regeneration,” he says.

Funding for this study came from the Hearing Health Foundation’s Hearing Restoration Project, Koerner Foundation and Sunnybrook Hearing Regeneration Initiative.

This blog was reposted with the permission of Sunnybrook Research Institute.
 

We need your help in funding the exciting work of hearing and balance scientists.

To donate today to support HHF's groundbreaking research,

please visit hhf.org/donate.

A Balancing Act

By Morgan Leppla

Balancing is pretty great. Not needing to think about how to stand upright is something I yield great benefit from, but is something that occurs without conscious effort or thought. I am fortunate, but many are not. This week is Balance Awareness Week, and HHF is highlighting the the inner ear and its mechanics!

The inner ear is a tiny but notable body part; not only is it important to hearing, but it is also where the balance organs and nerves are located.

The basic components of the inner ear include semicircular canals, the cochlea, the utricle, the saccule, and the vestibulocochlear nerve. The cochlea and one half of the vestibulocochlear nerve (the cochlear nerve) are in charge of hearing. The remaining semicircular canals, utricle, saccule, and vestibular nerve are responsible for balance.

There are three semicircular canals that contain fluid to activate sensory hair cells, which are arranged at ninety degree angles and detect different kinds of movement: up and down, side to side, and tilting. The utricle connects the semicircular canals to the saccule, which also detect motion. They are located in the vestibule inside of the labyrinth, which is the bony outer wall of the inner ear. All of this is the vestibular system.

But it is not only the vestibular system that assists with balance. Vision and sensory receptors (muscles, joints, skin, etc.) all transmit messages to the brain that work together and voila! balance.

Vestibular disorders can have a big effect on one’s equilibrium. People might experience dizziness, vertigo, or imbalance, as well as other inner ear-related issues. A commonly diagnosed  balance disorder is Meniere’s disease, which is one focus areas for our Emerging Research Grant (ERG) recipients.

Balance disorders can disrupt everyday life for those who experience them. It is also fairly common - in fact, about 69 million Americans or 35% of adults aged 40 and up have experiences vestibular dysfunction at some point in their life!

While it might be hard to believe something as tiny as the inner ear can affect a person’s ability to participate fully in daily life, HHF is fully committed to funding research that explores hearing and balance health.

Donate today to support groundbreaking research! 

We need your help in funding the exciting work of hearing and balance scientists.

Emerging Research Grants: 2017 Application Period is Now Open

Noise-Induced Brain Inflammation May Result in Painful Hearing

By Drs. Senthilvelan Manohar, Kelly Radziwon, and Richard Salvi

What do jet engines, sirens, and rock bands have in common? The sounds they emit are so intense that they are not only loud, but also painful, sometimes evoking a painful sensation around the external ear. The acoustic threshold for pain, 130-140 dB SPL, is intense enough to destroy or damage the delicate sensory hair cells, supporting cells and auditory nerve fibers in the inner ear. The axons from the auditory nerve deliver their messages to neurons located in the cochlear nuclei in the brainstem. 

In a recent paper published in Molecular and Cellular Neuroscience, Drs. Baizer and Manohar at the University at Buffalo were surprised to find that intense noise exposures that destroyed the sensory hair cells in the rat inner ear led to a prolonged period of auditory nerve fiber degeneration in the cochlear nucleus in the brainstem (Bazier et al., Neuroscience 303 (2015) 299–311). Nerve fiber degeneration was still occurring 6-9 months post-exposure, nearly a third of the rat’s lifespan. In brain regions where the fibers were degenerating, there was robust upregulation of brain immune cells (microglia), indicative of long-term neuro-inflammation triggered by the release of inflammatory molecules in the brain. Since sensory nerve fibers (e.g., pain, touch) from the face, head, neck and shoulders (facial, trigeminal and spinal nerves) enter the cochlear nucleus, the long-term neuro-inflammation occurring in this region could lower pain thresholds (hyperalgesia). If this were to occur, much lower, moderate-intensity sounds (60-80 dB) might be sufficient to cause hyperacusis (loudness intolerance) with ear pain.

With funding from the Hearing Health Foundation obtained by Drs. Radziwon* and Manohar to identify pain-related molecules in the auditory pathway as a result of noise exposure, Drs. Manohar, Adler, and Salvi carried out a second study in which they measured noise-induced changes in the expression (amount) of genes involved in the synthesis of proteins known to be involved in neuropathic pain and neuro- inflammation. Interestingly, the researchers found that intense noise exposure significantly altered the expression of six genes (Ccl12, Tlr2, Oprd1, II1b, Ntrk1 & Kcnq3) in the cochlear nucleus (Manohar et al., Molecular and Cellular Neuroscience 75 (2016) 101–112). These results suggest that noise-induced inflammation in the parts of the central auditory pathway that also processes sensory information related to pain might, in turn, activate the central pain pathway thus producing ear pain. Determining whether neuro-inflammation is directly responsible for ear pain will open the door for novel interventions to treat hearing loss and hyperacusis.

*Kelly Radziwon, Ph.D., is a 2015 Emerging Research Grants recipient. Her grant was generously funded by Hyperacusis Research Ltd. Learn more about Radziwon and her work in “Meet the Researcher.”
 

We need your help in funding the exciting work of hearing and balance scientists. Donate today to Hearing Health Foundation and support groundbreaking research: hhf.org/donate.

The Les Paul Foundation Funds Music Camps, Classroom Projects, Museums, Hearing Health Programs and Veterans' Recovery

New York, New York – July 11, 2016 - The Les Paul Foundation, whose mission is to honor the legacy of Les Paul, has continued its commitment to provide funding to projects that share Les Paul’s spirit. In 2016, the recipient organizations represent issues that were important to Les Paul and share Les Paul’s vision and innovation with their programs.

“Les Paul encouraged all of us to be innovative and create opportunities so the world would become a better place,” said Michael Braunstein, Executive Director of the Les Paul Foundation. “The organizations that have received grants perpetuate many of his philosophies and ideas. This allows us at the foundation to continue his legacy and show support for his values.”

Organizations that have benefitted from recent Les Paul Foundation grants include:

Birch Creek Music Performance Center of Egg Harbor, WI offers a summer guitar master class that includes Les Paul’s inventions, experiments and recording technique.

The Bonaroo Works Fund of Nashville, TN coordinated with the Les Paul Foundation to present the first ever Les Paul Spirit Award. The Bonaroo Works Fund supports education, music and arts programs for children or communities, protection of the environment and environment sustainability, and the arts/humanities in middle Tennessee.

The Boys & Girls Clubs of Martin County of Hobe Sound, FL weaves Les Paul’s contribution to rock and roll into their Les Rock program. Youth, ages 8 – 18, learn about Les’ contribution to music production including multi-tracking.

Camp Spin Off Foundation of Las Vegas, NV, provides 13-17 year olds an opportunity to learn about music production, remixing, music business and how to DJ. Campers learn how crucial Les Paul’s recording innovations were to how music is produced today.

Discovery World in Milwaukee, WI is reinforcing its Les Paul House of Sound exhibit with two new Les Paul-based school programs.

First Stage Milwaukee in Milwaukee, WI is sharing Les Paul’s stories of perseverance and innovation with elementary students. Through the dramatic process, students explore Les Paul’s inventions, his influence on the music industry, his creativity and his ability to overcome life’s challenges.

Hearing Education and Awareness for Rockers located in San Francisco, CA continues to include Les Paul in its presentations to music and sound arts schools and in its on-line presence. The organization focuses on encouraging youth to handle the power of sound in a safe manner.

The Hearing Health Foundation, headquartered in New York, NY, is the largest nonprofit supporter of hearing research. The Les Paul Foundation Award for Tinnitus Research is awarded annually to the most promising researcher studying the cause of ringing in the ears. This year’s recipient is Julia Campbell, Ph.D, Au.D, CCC-A, F-AAA, Assistant Professor, Communication Sciences and Disorders at The University of Texas at Austin.

“I am deeply honored to have received a grant award from the Les Paul Foundation to study brain function in the perception of tinnitus.  Tinnitus is a disorder that affects millions of people around the world, and yet we still have no way to measure this disorder or a cure for it.  Les Paul was an innovator, a dreamer, and a doer who loved to bring new sound into people’s lives.  I believe that his legacy is an inspiration to not only better understand tinnitus, but to use this knowledge to improve the quality of life in those it affects,” said Campbell.

Legacy Music Alliance in Salt Lake City, UT uses Les Paul’s story from the Les Paul Foundation website in guitar programs, which are taught in Utah’s schools. Musical instruments are purchased and provided to Utah schools for use by students.

Litchfield Music Alliance of Litchfield, CT hosts Nicki Parrott of the Les Paul Trio at its master classes. Nicki tells Les’ story and includes his music in her classes.

Mahwah Museum Society of Mahwah, NJ will be integrating digital technology into its permanent Les Paul exhibit to increase visitors’ access to documents, photos and videos of Les Paul.

Six String Heroes of Jefferson Barracks in O’Fallon, MO use music to help injured veterans heal physical and mental wounds. The group shares Les’ story of perseverance and how Les experienced the healing power of music.

VHI Save the Music of New York, NY receives funding for its program to reintroduce music into public schools across the United States through its supply of musical instruments to schools in need. Each school will receive copies of a student-friendly biography of Les Paul for use by students.

Waukesha Community Art Project of Waukesha, WI will relay Les Paul’s love of music and his unending curiosity and relentless search for answers to inspire students to ask their own questions and make their own discoveries.

Wisconsin School Music Association of Madison, WI will guide student musicians through the maze of music business so that they can succeed and protect their work. Les Paul’s story will illustrate for students how success comes from never giving up.

Women’s Audio Mission of San Francisco, CA focuses on advancing women in music production and technology. Les Paul’s story inspires students in their hands-on electronics projects. The organization aims to cultivate the female version of Les Paul.

For more information on the Les Paul Foundation go to www.lespaulfoundation.org. Join the conversation at www.facebook.com/lespaulfoundation or www.twitter.com/lespaulfoundation

Grant applications are accepted twice a year. http://www.lespaulfoundation.org/programs/.

PRESS CONTACT
Caroline Galloway

(440) 591-3807   caroline@m2mpr.com

Neural sensitivity to binaural cues with bilateral cochlear implants

By Massachusetts Eye and Ear/Harvard Medical School

Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears (interaural time difference, [ITD]) to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors.

 A team of researchers from Massachusetts Eye and Ear/Harvard Medical School, including past funded Emerging Research Grantee, Yoojin Chung, Ph.D., studied how the neurons in the auditory midbrain encode binaural cues delivered by bilateral CIs in an animal model. They found that the majority of neurons in the auditory midbrain were sensitive to ITDs, however, their sensitivity degraded with increasing pulse rate. This degradation paralleled pulse-rate dependence of perceptual limits in human CI users.

This study provides a better understanding of neural mechanisms underlying the limitation of current clinical bilateral CIs and suggests directions for improvement such as delivering ITD information in low-rate pulse trains.

The full paper was published in The Journal of Neuroscience and is available here. This article was republished with permission of the Massachusetts Eye and Ear/Harvard Medical School.

Dr. Yoojin Chung, Ph.D. was a 2012 and 2013 General Grand Chapter Royal Arch Masons International award recipient through our Emerging Research Grants program. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grantees 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.

Brain and Alzheimer's Disease Awareness Month

By Morgan Leppla

Bodies are complex systems, composed of many minute details. The human anatomy serves to remind us of the intricacies of our world. This June for Brain and Alzheimer’s Awareness Month, Hearing Health Foundation (HHF) invites you to join us in celebrating one of the most mysterious and fascinating part of the body: the brain.

For one to grasp the physiological complexity of being  human, one ought to understand how their body’s many systems work in tandem. For example, each person’s brain depends on stimulation to keep it in tip-top shape and and their bodies depend on their brains to function as they are intended to.

This is clearly a stripped down explanation of the role brains play. Of course an organism’s structure can be broken down into smaller and smaller parts, so let’s focus on one of special importance to us here at HHF, hearing.

Frank Lin, M.D., Ph.D., from Johns Hopkins University reports in 2014 that hearing loss affects brain structure, and specifically accelerates brain tissue loss. The study was conducted over a 10-year period with a sampling of people which included those with substantial hearing loss and those with normal hearing.  After analyzing years of magnetic resonance imaging scans, his conclusions suggest people with substantial hearing loss show higher rates of brain atrophy. Lin explains brain shrinkage could be the result of an “‘impoverished’ auditory cortex” since there is reduced brain stimulation in that area.

"If you want to address hearing loss well," Lin says, "you want to do it sooner rather than later. If hearing loss is potentially contributing to these differences we're seeing on an MRI, you want to treat it before these brain structural changes take place."

The human brain contains some of the most challenging biological mysteries in science (and always has). Unlocking those takes perseverance, so HHF thanks brain and hearing researchers for the time and energy devoted to rigorous research and ultimately revealing information critical to improving brain health.

Parts really do affect the health of the whole. So for the brain and beyond, please make an appointment with your hearing healthcare professional for your annual checkup and, if you are diagnosed with a hearing loss, managing it. More than just your hearing will benefit! Untreated hearing loss has been linked to dementia, depression, diabetes, falls, and heart disease.

Want to learn more about brain health? Check out last year’s blog here: Your Brain Is a Muscle: Use It or Lose It

NEWS UPDATE: Report on Hearing Health Care Released

By Morgan Leppla

Did you know it is estimated that 67 to 86 percent of people who might benefit from hearing aids do not have them? In a much-anticipated National Academies of Sciences, Engineering, and Medicine (NAS) report, published on June 2, 2016, NAS addresses the areas of hearing healthcare that currently prevent many of the 48 million Americans with hearing loss from seeking treatment, and provide 12 recommendations for improvement.

The NAS report recognizes that hearing loss detracts from individuals’ participation in family life, school, and work, and can affect anyone, young or old. People deserve the ability to communicate effectively, live healthily, and enjoy a high quality of life.

Specifically, the report recommends “key institutional, technological, and regulatory changes that would enable consumers to find and fully use the appropriate, affordable, high-quality services, technologies, and support they need.”

Currently, hearing healthcare is not focused on the consumer. However, through implementing the report’s recommendations, it would improve:

• The quality and affordability of hearing healthcare

• Access to accurate information that should be readily available to the public

• Increasing the number of options for consumers to choose from, in order to best fit individual needs

• Reducing stigma and bettering education

• Ending governmental measures that create obstacles to easy access

The NAS report further explains that this is everyone’s responsibility to manage their hearing health: Cross-sector, sustained collaboration is crucial to successful implementation of the report’s blueprint.

"Hearing Health Foundation (HHF) recommends everyone talk to their doctors to identify any hearing loss as well as to find the best hearing loss treatment for them. HHF is dedicated to funding research to cure and treat hearing loss and tinnitus  and is proud to play a role in pushing hearing and balance research forward,” says Nadine Dehgan, HHF CEO.

HHF would like to thank the NAS and its expert committee for their hard work in preparing this report, including the committee’s Judy R. Dubno, Ph.D., a member of HHF’s Board of Directors, and Debara L. Tucci, M.D., a member of HHF’s Council of Scientific Trustees. 

Hearing Aid Use Is Associated with Improved Cognitive Function in Hearing-Impaired Elderly

By Columbia University Medical Center

A study conducted by researchers at Columbia University Medical Center (CUMC) found that older adults who used a hearing aid performed significantly better on cognitive tests than those who did not use a hearing aid, despite having poorer hearing.

The study was published online in the American Journal of Geriatric Psychiatry.

The researchers also found that cognitive function was directly related to hearing ability in participants who did not use a hearing aid.

More than half of adults over age 75 have hearing loss, yet less than 15 percent of the hearing impaired use a hearing aid device. Previous studies have shown that the hearing-impaired elderly have a higher incidence of fall- and accident-related death, social isolation, and dementia than those without hearing loss. Studies have also demonstrated that hearing aid use can improve the social, functional, and emotional consequences of hearing loss.

“We know that hearing aids can keep older adults with hearing loss more socially engaged by providing an important bridge to the outside world,” said Anil K. Lalwani, MD, professor of otolaryngology/head and neck surgery at Columbia and otolaryngologist at NewYork-Presbyterian/CUMC and NewYork-Presbyterian/Morgan Stanley Children’s Hospital. “In this study, we wanted to determine if they could also slow the effects of aging on cognitive function.”

The study included 100 adults with hearing loss between the ages of 80 and 99. Of the participants, 34 regularly used a hearing aid. Audiometry tests were performed to measure the degree of hearing loss. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE), in which participants give vocal responses to verbal commands. Executive function was also assessed with the Trail Making Test, Part B (TMT-B), which does not have a verbal or auditory component.

Hearing aid users, who had worse hearing than non-users, performed significantly (1.9 points) better on the MMSE. Among non-users, participants with more hearing loss also had lower MMSE scores than those with better hearing. Although hearing aid users performed better than non-users on the TMT-B, the difference was not statistically significant. In addition, TMT-B scores were not correlated with hearing level.

“Our study suggests that using a hearing aid may offer a simple, yet important, way to prevent or slow the development of dementia by keeping adults with hearing loss engaged in conversation and communication,” said Dr. Lalwani.

This blog was reposted with the permission of Columbia University Medical Center. 

Anil K. Lalwani, M.D. is the Head of Hearing Health Foundation's Council of Scientific Trustees and sits on our Board of Directors. 

We need your help in funding the exciting work of hearing and balance scientists.

To donate today to support HHF's groundbreaking research,

please visit hhf.org/donate.