Study possible new treatments for hearing loss

Researchers have taken an important step toward what could become a new approach to restoring hearing loss. In a new study, published today in the European Journal of Neuroscience, scientists have been able to regenerate sensory hair cells in the cochlea, part of the inner ear, which convert sound vibrations into electrical signals and can be permanently lost due to damage from aging or noise

Hearing loss has long been recognized as a reality for the aging population: an estimated 30 million Americans have significant hearing loss. However, scientists have long observed that other animals, including birds, frogs and fish, have the ability to regenerate lost hair cells.

"It's funny, but mammals are the strange animal kingdom in terms of cochlear regeneration," said Jingyuan Zhang, Ph.D., of the Department of Biology at the University of Rochester and co-author of the study. "We are the only vertebrates that can not do it."

Research conducted in the laboratory of Patricia White, Ph.D. in 2012, has identified a family of receptors, called epidermal growth factor (EGF), responsible for the activation of the supporting cells in the auditory organs of the birds. When they are triggered, these cells proliferate and promote the generation of new sensory hair cells. She hypothesized that this signaling pathway could potentially be manipulated to produce a similar result in mammals. White is an associate professor of research at the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) and lead author of this study.

"In mice, the cochlea expresses EGF receptors throughout the animal's life, but they apparently never lead to regeneration of hair cells," White said. "Perhaps during mammalian evolution, there have been changes in the expression of intracellular regulators of EGF receptor family signaling." could have impaired the signaling result, blocking regeneration, promoting both regeneration of hair cells and their integration with nerve cells, two essential elements of hearing. "

In the new study, which involved researchers from the URMC and Massachusetts Ear and Eye Infirmary, part of Harvard Medical School, the team tested the theory that signaling from the family of EGF receptors may play a role in cochlear regeneration in mammals. The researchers focused on a specific receptor called ERBB2, present in cochlear support cells.

The researchers studied different methods to activate the EGF signaling pathway. A set of experiments involved the use of a virus to target ERBB2 receptors. Another mouse implicated genetically modified to overexpress an activated ERBB2. A third experiment was to test two drugs, known originally to stimulate the activity of stem cells in the eyes and pancreas, which activate ERBB2 signaling.

The researchers found that activation of the ERBB2 pathway triggered a series of cascading cellular events by which cochlear support cells began to proliferate and began the activation process of other neighboring stem cells to become new cells. sensory ciliates. Moreover, it appears that this process could not only have an impact on regeneration of sensory hair cells, but also promote their integration with nerve cells.

"The process of hearing repair is a complex problem and requires a series of cellular events," White said. "You need to regenerate sensory hair cells and these cells must function properly and connect to the necessary neural network.This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration restoration. # 39; audience. "

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More information:
Jingyuan Zhang et al., ERBB2 signaling supporting in vitro cell proliferation and the apparent formation of supernumerary hair cells in vivo in the neonatal mouse cochlea, European Journal of Neuroscience (2018). DOI: 10.1111 / ejn.14183