Newborn

A Balancing Act Before the Onset of Hearing

By Sonja J. Pyott, Ph.D.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

The development of the auditory system begins in the womb and culminates in a newborn’s ability to hear upon entering the world. While the age at which hearing begins varies across mammals, the sensory structures of the inner ears are active before the onset of hearing. This activity instructs the maturation of the neural connections between the inner ear and brain, an essential component of the proper development of hearing. However, we still know very little about the mechanisms regulating the activity of these sensory structures and their neural connections, specifically during the critical period just before the onset of hearing.

In our paper, “mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea,” soon to be published in an upcoming issue of The Journal of Physiology, we investigate the role of glutamate, a neurotransmitter, in regulating activity of the sensory structures and their connections in the inner ear before the start of hearing.

Neurotransmitters assist in the communication between neurons and are typically classified as either excitatory or inhibitory based on their action. Excitatory action results in stimulation; inhibitory action assists in the calming of the brain. Our research found that although glutamate typically excites activity, it also elicits inhibitory activity. This dual role for glutamate occurs because it activates two distinct classes of glutamate receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs).

Importantly, this dual activation balances excitatory and inhibitory activity of the sensory structures, a balance of which is likely important in the final refinement of the neural connections between the inner ear and brain prior to the onset of hearing.

As part of future research, we will further investigate the role of mGluRs, one the distinct classes of glutamate receptors, in the development of hearing. We will also investigate if mGluRs balance excitatory and inhibitory activity in the adult inner ear, similar to its role prior to the onset of hearing. Insights into these mechanisms may identify new ways to modulate activity and prevent congenital or acquired hearing loss.

Study coauthor Sonja J. Pyott, Ph.D., was a 2007 and 2008 Hearing Health Foundation Emerging Research Grants recipient.

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Life-Saving Antibiotics Increase Risk of Hearing Loss

By Oregon Health & Science University

Approximately 80% of infants in neonatal intensive care units receive antibiotics known to be toxic to the ear. 

Seeking to stem the tide of permanent hearing loss from the use of life saving antibiotics, researchers at Oregon Health & Science University have found that patients stricken with dangerous bacterial infections are at greater risk of hearing loss than previously recognized. Inflammation from the bacterial infections substantially increased susceptibility to hearing impairment by increasing the uptake of aminoglycoside antibiotics into the inner ear, the researchers report. Their findings are published in online in the journal Science-Translational Medicine.

“Currently, it’s accepted that the price that some patients have to pay for surviving a life-threatening bacterial infection is the loss of their ability to hear. We must swiftly bring to clinics everywhere effective alternatives for treating life-threatening infections that do not sacrifice patients’ ability to hear,” said Peter S. Steyger, Ph.D.*, professor of otolaryngology, head and neck surgery, Oregon Hearing Research Center, Oregon Health & Science University School of Medicine. “Most instances in which patients are treated with aminoglycosides involve infants with life-threatening infections. The costs of this incalculable loss are borne by patients and society. When infants lose their hearing, they begin a long and arduous process to learn to listen and speak. This can interfere with their educational trajectory and psychosocial development, all of which can have a dramatic impact on their future employability, income and quality of life.”

Aminoglycosides, antimicrobials that are indispensable to treating life-threatening bacterial infections, are toxic to the ear. Relied on by physicians to treat meningitis, bacteremia and respiratory infections in cystic fibrosis, aminoglycosides kill the sensory cells in the inner ear that detect sound and motion.

Infants in neonatal intensive care units, or NICUs, are at particular risk. Each year, approximately 80 percent of 600,000 admissions into NICUs in the United States receive aminoglycosides. The rate of hearing loss in NICU graduates is 2 to 4 percent compared with 0.1 to 0.3 percent of full-term births from congenital causes of hearing loss.

When Steyger and colleagues gave healthy mice a low amount of aminoglycoside, the rodents experienced a small degree of hearing loss. If the mice had an inflammation that is typical of the infections treated with aminoglycosides in humans, the mice experienced a vastly greater degree of hearing loss.

The study lays the groundwork for improving the standard of care guidelines for patients receiving aminoglycosides. To shield patients’ hearing, the researchers called for the development of more targeted aminoglycosides and urged clinicians to choose more targeted, non-ototoxic antibiotics or anti-infective drugs to treat patients stricken with severe infections.

Due to their widespread availability and low cost, aminoglycosides are used frequently worldwide. Clinical use of aminoglycosides is limited due to the known risk of acute kidney poisoning and permanent hearing loss, yet are crucial life-savers in cases with potentially fatal infections.

Scientists who contributed to the OHSU study, “Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity,” include: Steyger; Ja-won Koo, M.D., Ph.D.; Lourdes Quintanilla-Dieck, M.D.; Meiyan Jiang, Ph.D.; Jianping Liu, M.D., Ph.D.; Zachary D. Urdang, B.S.; Jordan Allensworth, B.S.; Campbell P. Cross, B.A.; and Hongzhe Li, Ph.D.

This research was supported by: National Research Foundation of Korea grant 2011-0010166; Seoul National University Bundang Hospital 03-2011-007 (J.K.W.); National Institute of Deafness and Other Communication Disorders R01 DC004555, R01 DC12588 (P.S.S.), R03 DC011622 (H.L.), and P30 DC005983; and the Department of Otolaryngology at OHSU (L.Q.D.).

*Peter S. Steyger, Ph.D., is a prior Hearing Health Foundation board member and previous head of our Council of Scientific Trustees.

The above post is reprinted from materials provided by Oregon Health & Science University.

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