Navigation Links
Zebrafish provide useful screening tool for genes, drugs that protect against hearing loss
Date:2/29/2008

A small striped fish is helping scientists understand what makes people susceptible to a common form of hearing loss, although, in this case, its not the fishs ears that are of interest. In a study published in the Feb. 29 issue of the journal PLoS Genetics, researchers at the University of Washington have developed a research method that relies on a zebrafishs lateral linethe faint line running down each side of a fish that enables it to sense its surroundingsto quickly screen for genes and chemical compounds that protect against hearing loss from some medications. The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health.

The fishs lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fishs body, making them more easily accessible, said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. This means that scientists can very efficiently analyze the sensory structures under different conditions to find out what is likely to cause damage to these structures and, conversely, what can protect them from damage.

When people are exposed to some antibiotics and chemotherapy agents, the sensory structures in the inner ear, called hair cells, can be irreversibly damaged, resulting in hearing loss and balance problems. Such medications are called ototoxic. People vary widely in their susceptibility to these agents as well as to damage caused by other chemical agents, loud sounds and aging.

To find out why this is so, senior scientists Edwin Rubel, Ph.D., David Raible, Ph.D. and their research team developed a screening strategy that uses hair cells in the lateral line of zebrafish larvae to signal how hair cells in a persons inner ear might respond under similar conditions. Hair cells are named for small bristly extensions, or stereocilia, jutting from their tops. Movement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fishs environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.

The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.

Using genetic techniques, the group then examined the larvaes DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutationseach located on different genesthat, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.

Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening techniqueexposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cellsthe researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouses inner ear against the drug, indicating that the same compound may be protective for other mammals as well.

One of the pluses about working with zebrafish is that, like other fish, they produce hundreds of offspring. We can look at lots of animals and we can look at many hair cells per animal, which means that we can get good quantitative data, said Dr. Raible.

The authors suggest that their research technique, which combines chemical screening with traditional genetic approaches, offers a fast and efficient way to identify potential drugs and drug targets that may one day provide therapies for people with hearing loss and balance disorders.


'/>"/>

Contact: Jennifer Wenger
jwenger@mail.nih.gov
301-496-7243
NIH/National Institute on Deafness and Other Communication Disorders
Source:Eurekalert

Related medicine news :

1. Phylonix granted broad European patent for transplanting human cells into zebrafish
2. Transparent zebrafish help researchers track breast cancer
3. NIH awards Phylonix phase II SBIR to develop zebrafish models for eye diseases
4. Microbiotic technology developed for microinjection of zebrafish embryos
5. Johnson & Johnson Diabetes Institute, LLC Launches New Center to Provide State-of-the-Art Education, Training to Health Professionals
6. Crdentia Selected by Leading Staffing Vendor to Provide Health Care Staffing Services to One of the Largest Hospital Chains in the U.S.
7. Hooper Holmes to Provide Business Update
8. XCPT(TM) Patient Engagement and Communication Software and DentalXP.com, a Leading Provider of Online Dental Education and Content, Sign a Co-Marketing Agreement
9. AMN Healthcare Reports Fourth Quarter and Year End 2007 Results; Provides Full Year 2008 Guidance
10. HASP Online Provides Free Job Safety Analysis Tool Available Online
11. Microsoft to Showcase Innovative Solutions for Healthcare Providers and Consumers at HIMSS 2008 Annual Conference & Exhibition
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... ... issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the ... several important health care topics including advance care planning, healthcare costs and patient ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/24/2016)... ... ... Those who have experienced traumatic events may suffer from a complex set of ... or alcohol abuse, as a coping mechanism. To avoid this pain and suffering, Serenity ... event. , Trauma sufferers tend to feel a range of emotions, from depression, guilt, ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... now offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with ... Damon brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty Network, ... M. Weintraub as a prominent plastic surgeon and the network’s newest partner. ... the most handsome men, look naturally attractive. Plastic surgery should be invisible.” He ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new affiliate with operations headquartered in ... America . ... ... ... ...
(Date:6/23/2016)... , June 23, 2016  Guerbet announced today that ... Supplier Horizon Award . One of ... was recognized for its support of Premier members through ... clinical excellence, and commitment to lower costs. ... this recognition of our outstanding customer service from Premier," ...
(Date:6/23/2016)... , June 23, 2016 Research ... "Surgical Procedure Volumes: Global Analysis (United States, China, Japan, ... report to their offering. ... tool for healthcare business planners, provides surgical procedure volume ... surgery trends with an in-depth analysis of growth drivers ...
Breaking Medicine Technology: