cochlea – NIH Director's Blog (original) (raw)
A Potential New Way to Prevent Noise-Induced Hearing Loss: Trapping Excess Zinc
Posted on February 22nd, 2024 by Dr. Monica M. Bertagnolli
Zinc in the inner ear is concentrated in stereocilia essential for hearing, but a new study finds that loud sounds cause damaging dysregulation of the essential mineral that can lead to noise-induced hearing loss. Credit: Donny Bliss/NIH
Hearing loss is a pervasive problem, affecting one in eight people aged 12 and up in the U.S.1 While hearing loss has multiple causes, an important one for millions of people is exposure to loud noises, which can lead to gradual hearing loss, or people can lose their hearing all at once. The only methods used to prevent noise-induced hearing loss today are avoiding loud noises altogether or wearing earplugs or other protective devices during loud activities. But findings from an intriguing new NIH-supported study exploring the underlying causes of this form of hearing loss suggest it may be possible to protect hearing in a different way: with treatments targeting excess and damaging levels of zinc in the inner ear.
The new findings, reported in the Proceedings of the National Academy of Sciences, come from a team led by Thanos Tzounopoulos, Amantha Thathiah, and Chris Cunningham, at the University of Pittsburgh.2 The research team is focused on understanding how hearing works, as well as developing ways to treat hearing loss and tinnitus (the perception of sound, like ringing or buzzing, that doesn’t have an external source), which both can arise from loud noises.
Previous studies have shown that traumatic noises of varying durations and intensities can lead to different types of damage to cells in the cochlea, the fluid-filled cavity in the inner ear that plays an essential role in hearing. For instance, in mouse studies, noise equivalent to a blasting rock concert caused the loss of tiny sound-detecting hair cells and essential supporting cells in the cochlea, leading to hearing loss. Milder noises comparable to the sound of a hand drill can lead to subtler hearing loss, as essential connections, or synapses, between hair cells and sensory neurons are lost.
To better understand why this happens, the research team wanted to investigate the underlying cellular- and molecular-level events and signals responsible for inner ear damage and irreversible hearing loss caused by loud sounds. They looked to zinc, an essential mineral in our diets that plays many important roles in the body. Interestingly, zinc concentrations in the inner ear are highest of any organ or tissue in the body. But, despite this, the role of zinc in the cochlea and its effects on hearing and hearing loss hadn’t been studied in detail.
Most zinc in the body—about 90%—is bound to proteins. But the researchers were interested in the approximately 10% of zinc that’s free-floating, due to its important role in signaling in the brain and other parts of the nervous system. They wanted to find out what happens to the high concentrations of zinc in the mouse cochlea after traumatic levels of noise, and whether targeting zinc might influence inner ear damage associated with hearing loss.
The researchers found that, hours after mice were exposed to loud noise, zinc levels in the inner ear spiked and were dysregulated in the hair cells and in key parts of the cochlea, with significant changes to their location inside cells. Those changes in zinc were associated with cellular damage and disrupted communication between sensory cells in the inner ear.
The good news is that this discovery suggested a possible solution: inner ear damage and hearing loss might be averted by targeting excess zinc. And their subsequent findings suggest that it works. Studies in mice that were treated with a slow-releasing compound in the inner ear were protected from noise-induced damage and associated hearing loss. The treatment involves a chemical compound known as a zinc chelating agent, which binds and traps excess free zinc, thus limiting cochlear damage and hearing loss.
Will this strategy work in people? We don’t know yet. However, the researchers report that they’re planning to pursue preclinical safety studies of the new treatment approach. Their hope is to one day make a zinc-targeted treatment readily available to protect against noise-induced hearing loss. But, for now, the best way to protect your hearing while working with noisy power tools or attending a rock concert is to remember your ear protection.
References:
[1] Quick Statistics About Hearing. National Institute on Deafness and Other Communication Disorders.
[2] Bizup B, et al. Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery. PNAS. DOI: 10.1073/pnas.2310561121 (2024).
NIH Support: National Institute on Deafness and Other Communication Disorders, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering
A Nose for Science
Posted on May 23rd, 2019 by Dr. Francis Collins
Credit: Lu Yang, David Ornitz, and Sung-Ho Huh, Washington University School of Medicine, St. Louis; University of Nebraska Medical Center, Omaha
Our nose does a lot more than take in oxygen, smell, and sometimes sniffle. This complex organ also helps us taste and, as many of us notice during spring allergy season when our noses get stuffy, it even provides some important anatomic features to enable us to speak clearly.
This colorful, almost psychedelic image shows the entire olfactory epithelium, or “smell center,” (green) inside the nasal cavity of a newborn mouse. The olfactory epithelium drapes over the interior walls of the nasal cavity and its curvy bony parts (red). Every cell in the nose contains DNA (blue).
The olfactory epithelium detects odorant molecules in the air, providing a sense of smell. In humans, the nose has about 400 types of scent receptors, and they can detect at least 1 trillion different odors [1].
But this is more than just a cool image captured by graduate student Lu Yang, who works with David Ornitz at Washington University School of Medicine, St. Louis. The two discovered a new type of progenitor cell, called a FEP cell, that has the capacity to generate the entire smell center [2]. Progenitor cells are made by stem cells. But they are capable of multiplying and producing various cells of a particular lineage that serve as the workforce for specialized tissues, such as the olfactory epithelium.
Yang and Ornitz also discovered that the FEP cells crank out a molecule, called FGF20, that controls the growth of the bony parts in the nasal cavity. This seems to regulate the size of the olfactory system, which has fascinating implications for understanding how many mammals possess a keener sense of smell than humans.
But it turns out that FGF20 does a lot more than control smell. While working in Ornitz’s lab as a postdoc, Sung-Ho Huh, now an assistant professor at the University of Nebraska Medical Center, Omaha, discovered that FGF20 helps form the cochlea [3]. This inner-ear region allows us to hear, and mice born without FGF20 are deaf. Other studies show that FGF20 is important for development of the kidney, teeth, mammary gland, and of specific types of hair [4-7]. Clearly, this indicates multi-tasking can be a key feature of a protein, not a trivial glitch.
The image was one of the winners in the 2018 BioArt Scientific Image & Video Competition, sponsored by the Federation of American Societies for Experimental Biology (FASEB). Its vibrant colors help to show the basics of smell, and remind us that every scientific picture tells a story.
References:
[1] Humans can discriminate more than 1 trillion olfactory stimuli. Bushdid C1, Magnasco MO, Vosshall LB, Keller A. Science. 2014 Mar 21;343(6177):1370-1372.
[2] FGF20-Expressing, Wnt-Responsive Olfactory Epithelial Progenitors Regulate Underlying Turbinate Growth to Optimize Surface Area. Yang LM, Huh SH, Ornitz DM. Dev Cell. 2018;46(5):564-580.
[3] Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal. Huh SH, Jones J, Warchol ME, Ornitz DM. PLoS Biol. 2012;10(1):e1001231.
[4] FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Barak H, Huh SH, Chen S, Jeanpierre C, Martinovic J, Parisot M, Bole-Feysot C, Nitschke P, Salomon R, Antignac C, Ornitz DM, Kopan R. Dev. Cell. 2012;22(6):1191-1207
[5] Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty. Elo T, Lindfors PH, Lan Q, Voutilainen M, Trela E, Ohlsson C, Huh SH, Ornitz DM, Poutanen M, Howard BA, Mikkola ML. Sci Rep. 2017;7(1):5049
[6] Ectodysplasin regulates activator-inhibitor balance in murine tooth development through Fgf20 signaling. D Haara O, Harjunmaa E, Lindfors PH, Huh SH, Fliniaux I, Aberg T, Jernvall J, Ornitz DM, Mikkola ML, Thesleff I. Development. 2012;139(17):3189-3199.
[7] Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles. Huh SH, Närhi K, Lindfors PH, Häärä O, Yang L, Ornitz DM, Mikkola ML. Genes Dev. 2013;27(4):450-458.
Links:
Taste and Smell (National Institute on Deafness and Other Communication Disorders/NIH)
Ornitz Lab, (Washington University, St. Louis)
Huh Lab, (University of Nebraska Medical Center, Omaha)
BioArt Scientific Image & Video Competition, (Federation of American Societies for Experimental Biology, Bethesda, MD)
NIH Support: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders
Posted In: Snapshots of Life
Tags: 2018 BioArt Scientific Image & Video Competition, cochlea, FASEB, FEP cell, FGF20, hearing, nasal cavity, nose, odor, olfactory epithelium, olfactory system, progenitor cells, smell