PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Scientists restore hearing in noise-deafened mice, pointing way to new therapies

U-M-led team shows key role of protein called NT3 in ear-to-brain communication, and as a target for future treatments

Scientists restore hearing in noise-deafened mice, pointing way to new therapies
2014-10-21
(Press-News.org) ANN ARBOR, Mich. — Scientists have restored the hearing of mice partly deafened by noise, using advanced tools to boost the production of a key protein in their ears.

By demonstrating the importance of the protein, called NT3, in maintaining communication between the ears and brain, these new findings pave the way for research in humans that could improve treatment of hearing loss caused by noise exposure and normal aging.

In a new paper in the online journal eLife, the team from the University of Michigan Medical School's Kresge Hearing Research Institute and Harvard University report the results of their work to understand NT3's role in the inner ear, and the impact of increased NT3 production on hearing after a noise exposure.

Their work also illustrates the key role of cells that have traditionally been seen as the "supporting actors" of the ear-brain connection. Called supporting cells, they form a physical base for the hearing system's "stars": the hair cells in the ear that interact directly with the nerves that carry sound signals to the brain. This new research identifies the critical role of these supporting cells along with the NT3 molecules that they produce.

NT3 is crucial to the body's ability to form and maintain connections between hair cells and nerve cells, the researchers demonstrate. This special type of connection, called a ribbon synapse, allows extra-rapid communication of signals that travel back and forth across tiny gaps between the two types of cells.

"It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it's due to noise or normal aging," says Gabriel Corfas, Ph.D., who led the team and directs the U-M institute. "We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people. It's very exciting."

Using a special genetic technique, the researchers made it possible for some mice to produce additional NT3 in cells of specific areas of the inner ear after they were exposed to noise loud enough to reduce hearing. Mice with extra NT3 regained their ability to hear much better than the control mice.

Now, says Corfas, his team will explore the role of NT3 in human ears, and seek drugs that might boost NT3 action or production. While the use of such drugs in humans could be several years away, the new discovery gives them a specific target to pursue.

Corfas, a professor and associate chair in the U-M Department of Otolaryngology, worked on the research with first author Guoqiang Wan, Ph.D., Maria E. Gómez-Casati, Ph.D., and others in his former institution, Harvard. Some of the authors now work with Corfas in his new U-M lab. They set out to find out how ribbon synapses – which are found only in the ear and eye – form, and what molecules are important to their formation and maintenance.

Anyone who has experienced problems making out the voice of the person next to them in a crowded room has felt the effects of reduced ribbon synapses. So has anyone who has experienced temporary reduction in hearing after going to a loud concert. The damage caused by noise – over a lifetime or just one evening – reduces the ability of hair cells to talk to the brain via ribbon synapse connections with nerve cells.

Targeted Genetics Made Discovery Possible

After determining that inner ear supporting cells supply NT3, the team turned to a technique called conditional gene recombination to see what would happen if they boosted NT3 production by the supporting cells. The approach allows scientists to activate genes in specific cells, by giving a dose of a drug that triggers the cell to "read" extra copies of a gene that had been inserted into them. For this research, the scientists activated the extra NT3 genes only into the inner ear's supporting cells.

The genes didn't turn on until the scientists wanted them to – either before or after they exposed the mice to loud noises. The scientists turned on the NT3 genes by giving a dose of the drug tamoxifen, which triggered the supporting cells to make more of the protein. Before and after this step, they tested the mice's hearing using an approach called auditory brainstem response or ABR – the same test used on humans.

The result: the mice with extra NT3 regained their hearing over a period of two weeks, and were able to hear much better than mice without the extra NT3 production. The scientists also did the same with another nerve cell growth factor, or neurotrophin, called BDNF, but did not see the same effect on hearing.

Next Steps

Now that NT3's role in making and maintaining ribbon synapses has become clear, Corfas says the next challenge is to study it in human ears, and to look for drugs that can work like NT3 does. Corfas has some drug candidates in mind, and hopes to partner with industry to look for others.

Boosting NT3 production through gene therapy in humans could also be an option, he says, but a drug-based approach would be simpler and could be administered as long as it takes to restore hearing.

Corfas notes that the mice in the study were not completely deafened, so it's not yet known if boosting NT3 activity could restore hearing that has been entirely lost. He also notes that the research may have implications for other diseases in which nerve cell connections are lost – called neurodegenerative diseases. "This brings supporting cells into the spotlight, and starts to show how much they contribute to plasticity, development and maintenance of neural connections," he says.

INFORMATION:

In addition to Corfas, Wan and Gómez-Casati, who now works in Argentina, the research was performed by Angelica R. Gigliello, and M. Charles Liberman, Ph.D. director of the Eaton-Peabody Laboratories of the Massachusetts Eye and Ear Infirmary. The research was supported by the National Institute on Deafness and Other Communication Disorders (DC004820, DC005209) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655), both part of the National Institutes of Health, and by the Hearing Health Foundation.

Reference: eLife, http://elifesciences.org/content/early/2014/10/17/eLife.03564


[Attachments] See images for this press release:
Scientists restore hearing in noise-deafened mice, pointing way to new therapies

ELSE PRESS RELEASES FROM THIS DATE:

Penn researchers untangle the biological effects of blue light

Penn researchers untangle the biological effects of blue light
2014-10-21
PHILADELPHIA – Blue light can both set the mood and set in motion important biological responses. Researchers at the University of Pennsylvania's School of Medicine and School of Arts and Sciences have teased apart the separate biological responses of the human eye to blue light, revealing an unexpected contest for control. Their work addresses the properties of melanopsin, a light-sensitive protein in the eye that establishes the rhythm of our day-night cycle and the familiar constriction of the pupil to bright light. They measured the pupil response to stimulation ...

Study suggests altering gut bacteria might mitigate lupus

2014-10-21
WASHINGTON, DC – October 20, 2014 -- Lactobacillus species, commonly seen in yogurt cultures, correlate, in the guts of mouse models, with mitigation of lupus symptoms, while Lachnospiraceae, a type of Clostridia, correlate with worsening, according to research published ahead of print in Applied and Environmental Microbiology. "Our results suggest that the same investigation shold be performed in human subjects with lupus," says principal investigator Xin Luo of Virginia Tech, Blacksburg, VA. In the study, the investigators first showed that mouse models of lupus ...

NASA's HS3 mission continues with flights over Hurricane Gonzalo

NASAs HS3 mission continues with flights over Hurricane Gonzalo
2014-10-21
Tropical Storm Gonzalo strengthened into a hurricane on Oct. 14 when it was near Puerto Rico and provided a natural laboratory for the next phase of NASA's HS3 or Hurricane and Severe Storm Sentinel mission. The WB-57 aircraft flew over Hurricane Gonzalo on Oct. 15 carrying two HS3 mission instruments called HIWRAP and HIRAD in addition to a new Office of Naval Research sponsored dropsonde system. The WB-57 is a mid-wing, long-range aircraft capable of operation for extended periods of time from sea level to altitudes in excess of 60,000 feet. Two crew members are positioned ...

For prescription drug addiction treatment, buprenorphine maintenance trumps detoxification

2014-10-20
For treating patients with prescription opioid dependence in primary care, buprenorphine maintenance therapy is superior to detoxification, according to a new study by Yale School of Medicine researchers published in the Oct. 20 issue of JAMA Internal Medicine. Prescription opioid dependence has been increasing for the last 15 years and now surpasses heroin dependence. Doctors are also writing more prescriptions for pain management, which has led to higher experimentation and addiction rates, according to lead author David Fiellin, M.D., professor of internal medicine ...

New tracers can identify frac fluids in the environment

New tracers can identify frac fluids in the environment
2014-10-20
Scientists have developed new geochemical tracers that can identify hydraulic fracturing flowback fluids that have been spilled or released into the environment. The tracers have been field-tested at a spill site in West Virginia and downstream from an oil and gas brine wastewater treatment plant in Pennsylvania. "By characterizing the isotopic and geochemical fingerprints of enriched boron and lithium in flowback water from hydraulic fracturing, we can now track the presence of 'frac' fluids in the environment and distinguish them from wastewater coming from other ...

Supercomputers link proteins to drug side effects

2014-10-20
LIVERMORE, Calif. – New medications created by pharmaceutical companies have helped millions of Americans alleviate pain and suffering from their medical conditions. However, the drug creation process often misses many side effects that kill at least 100,000 patients a year, according to the journal Nature. Lawrence Livermore National Laboratory researchers have discovered a high-tech method of using supercomputers to identify proteins that cause medications to have certain adverse drug reactions (ADR) or side effects. They are using high-performance computers ...

Stress-related inflammation may increase risk for depression

2014-10-20
Preexisting differences in the sensitivity of a key part of each individual's immune system to stress confer a greater risk of developing stress-related depression or anxiety, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published October 20 in the Proceedings of the National Academy of Sciences (PNAS). Inflammation is the immune system's response to infection or disease, and has long been linked to stress. Previous studies have found depression and anxiety to be associated with elevated blood levels of inflammatory molecules ...

Built-in billboards: Male bluefin killifish signal different things with different fins

Built-in billboards: Male bluefin killifish signal different things with different fins
2014-10-20
CHAMPAIGN, Ill. — They help fish swim, but fins also advertise a fish's social standing and health. In a new study, researchers report that for the male bluefin killifish (Lucania goodei), each colorful fin presents its own messages to other fish. Researchers report their findings in the journal Behavioral Ecology. They're called "bluefin" killifish, but the first thing University of Illinois animal biology professor Rebecca Fuller noticed while she was snorkeling in a Florida stream was the killifishes' differently colored fins. In addition to having reflective ...

Patients who have left breast tumors have comparable OS to those with right breast tumors

2014-10-20
Fairfax, Va., October 20, 2014—Tumor laterality (left-side vs. right-side) does not impact overall survival in breast cancer patients treated with breast-conserving surgery and adjuvant external beam radiation therapy, according to a study published in the October 1, 2014 issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). Studies have shown that breast cancer patients treated with radiation therapy have improved local-regional recurrence, ...

Tarantula toxin is used to report on electrical activity in live cells

Tarantula toxin is used to report on electrical activity in live cells
2014-10-20
VIDEO: The movie is quantitative imaging of cells with potassium channels, bathed in dilute fluorescent tarantula toxin. Pixel color indicates intensity of tarantula toxin concentration. The circular shapes are cell surfaces,... Click here for more information. WOODS HOLE, Mass.--A novel probe that reports on the electrical activity of cells, made by fusing tarantula toxin with a fluorescent compound, is described in a paper today by scientists from the University of California, ...

LAST 30 PRESS RELEASES:

Genetic causes of cerebral palsy uncovered through whole-genome sequencing

Modesty and boastfulness – perception depends on usual performance

Do sweeteners increase your appetite? New evidence from randomised controlled trial says no 

Women with obesity do not need to gain weight during pregnancy, new study suggests

Individuals with multiple sclerosis face substantially greater risk of hospitalisation and death from COVID-19, despite high rates of vaccination

Study shows obesity in childhood associated with a more than doubling of risk of developing multiple sclerosis in early adulthood

Rice Emerging Scholars Program receives $2.5M NSF grant to boost STEM education

Virtual rehabilitation provides benefits for stroke recovery

Generative AI develops potential new drugs for antibiotic-resistant bacteria

Biofuels could help island nations survive a global catastrophe, study suggests

NJIT research team discovering how fluids behave in nanopores with NSF grant

New study shows association of historical housing discrimination and shortfalls in colon cancer treatment

Social media use may help to empower plastic surgery patients

Q&A: How to train AI when you don't have enough data

Wayne State University researchers uncover potential treatment targets for Zika virus-related eye abnormalities

Discovering Van Gogh in the wild: scientists unveil a new gecko species

Small birds spice up the already diverse diet of spotted hyenas in Namibia

Imaging detects transient “hypoxic pockets” in the mouse brain

Dissolved organic matter could be used to track and improve the health of freshwaters

Indoor air quality standards in public buildings would boost health and economy, say international experts

Positive associations between premenstrual disorders and perinatal depression

New imaging method illuminates oxygen's journey in the brain

Researchers discover key gene for toxic alkaloid in barley

New approach to monitoring freshwater quality can identify sources of pollution, and predict their effects

Bidirectional link between premenstrual disorders and perinatal depression

Cell division quality control ‘stopwatch’ uncovered

Vaccine protects cattle from bovine tuberculosis, may eliminate disease

Andrew Siemion to receive the SETI Institute’s 2024 Drake Award

New study shows how the Crimean-Congo hemorrhagic fever virus enters our cells

Neoadjuvant chemotherapy proves effective for locally advanced penile squamous cell carcinoma

[Press-News.org] Scientists restore hearing in noise-deafened mice, pointing way to new therapies
U-M-led team shows key role of protein called NT3 in ear-to-brain communication, and as a target for future treatments