Effect of pH on Development of the Zebrafish Inner Ear and Lateral Line: Comparisons between High School and University Settings.

Increasing carbon dioxide levels associated with climate change will likely have a devastating effect on aquatic ecosystems. Aquatic environments sequester carbon dioxide, resulting in acidic conditions that can negatively affect fish development. Increasing climate change impacts in the coming decades will have an outsized effect on younger generations.

Age-related changes in the zebrafish and killifish inner ear and lateral line.

Age-related hearing loss (ARHL) is a debilitating disorder for millions worldwide. While there are multiple underlying causes of ARHL, one common factor is loss of sensory hair cells. In mammals, new hair cells are not produced postnatally and do not regenerate after damage, leading to permanent hearing impairment.

Hepatocyte growth factor mimetic confers protection from aminoglycoside-induced hair cell death in vitro.

Loss of sensory hair cells from exposure to certain licit drugs, such as aminoglycoside antibiotics, can result in permanent hearing damage. Exogenous application of the neurotrophic molecule hepatocyte growth factor (HGF) promotes neuronal cell survival in a variety of contexts, including protecting hair cells from aminoglycoside ototoxicity. HGF itself is not an ideal therapeutic due to a short half-life and limited blood-brain barrier permeability.

On the value of diverse organisms in auditory research: From fish to flies to humans.

Historically, diverse organisms have contributed to our understanding of auditory function. In recent years, the laboratory mouse has become the prevailing non-human model in auditory research, particularly for biomedical studies. There are many questions in auditory research for which the mouse is the most appropriate (or the only) model system available.

Reproductive state modulates utricular auditory sensitivity in a vocal fish.

The plainfin midshipman, , is a seasonally breeding vocal fish that relies on acoustic communication to mediate nocturnal reproductive behaviors. Reproductive females use their auditory senses to detect and localize "singing" males that produce multiharmonic advertisement (mate) calls during the breeding season. Previous work showed that the midshipman saccule, which is considered the primary end organ used for hearing in midshipman and most other fishes, exhibits reproductive state and hormone-dependent changes that enhance saccular auditory sensitivity.

Putative COVID-19 therapies imatinib, lopinavir, ritonavir, and ivermectin cause hair cell damage: A targeted screen in the zebrafish lateral line.

The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials.

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings.

Over 100 drugs and chemicals are associated with permanent hearing loss, tinnitus, and vestibular deficits, collectively known as ototoxicity. The ototoxic potential of drugs is rarely assessed in pre-clinical drug development or during clinical trials, so this debilitating side-effect is often discovered as patients begin to report hearing loss. Furthermore, drug-induced ototoxicity in adults, and particularly in elderly patients, may go unrecognized due to hearing loss from a variety of etiologies because of a lack of baseline assessments immediately prior to novel therapeutic treatment.

Molecular and cellular responses to long-term sound exposure in peled (Coregonus peled).

This research examined the impacts of acoustic stress in peled (Coregonus peled Gmelin, 1788), a species commonly cultivated in Russia. This study presents a comparative analysis of the macula sacculi and otoliths, as well as primary hematological and secondary telomere stress responses, in control and sound-exposed peled. The authors measured the effects of long-term (up to 18 days) exposure to a 300 Hz tone at mean sound pressure levels of 176-186 dB re 1 μPa (SPL); the frequency and intensity were selected to approximate loud acoustic environments associated with cleaning equipment in aquaculture settings.

Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death.

Hearing loss is the third most common chronic health condition in the United States and largely results from damage to sensory hair cells. Major causes of hair cell damage include aging, noise exposure, and medications such as aminoglycoside antibiotics. Due to their potent antibacterial properties and low cost, aminoglycosides are often used for the treatment of gram-negative bacterial infections, surpassing expensive antibiotics with fewer harmful side effects.

Melanosome maturation proteins Oca2, Mitfa and Vps11 are differentially required for cisplatin resistance in zebrafish melanocytes.

Melanoma is the deadliest form of skin cancer, partially due to its inherent resistance to therapy. Here, we test in live larvae the hypothesis that mature melanosomes contribute to resistance to chemotherapeutic drug, cisplatin, via drug sequestration. We also compare three melanosome biogenesis proteins-microphthalmia-associated transcription factor (Mitfa), vacuolar protein sorting 11 (Vps11) and oculocutaneous albinism 2 (Oca2) to determine their respective contributions to chemoresistance.

Glucococorticoid receptor activation exacerbates aminoglycoside-induced damage to the zebrafish lateral line.

Aminoglycoside antibiotics have potent antibacterial properties but cause hearing loss in up to 25% of patients. These drugs are commonly administered in patients with high glucocorticoid stress hormone levels and can be combined with exogenous glucocorticoid treatment. However, the interaction of stress and aminoglycoside-induced hearing loss has not been fully explored.

Larval Zebrafish Lateral Line as a Model for Acoustic Trauma.

Excessive noise exposure damages sensory hair cells, leading to permanent hearing loss. Zebrafish are a highly tractable model that have advanced our understanding of drug-induced hair cell death, yet no comparable model exists for noise exposure research. We demonstrate the utility of zebrafish as model to increase understanding of hair cell damage from acoustic trauma and develop protective therapies.

Urban stormwater runoff negatively impacts lateral line development in larval zebrafish and salmon embryos.

After a storm, water often runs off of impervious urban surfaces directly into aquatic ecosystems. This stormwater runoff is a cocktail of toxicants that have serious effects on the ecological integrity of aquatic habitats. Zebrafish that develop in stormwater runoff suffer from cardiovascular toxicity and impaired growth, but the effects of stormwater on fish sensory systems are not understood.

PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line.

Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood.

Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage Lateral Line Hair Cells.

Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products.

Hearing sensitivity differs between zebrafish lines used in auditory research.

Zebrafish are increasingly used in auditory studies, in part due to the development of several transgenic lines that express hair cell-specific fluorescent proteins. However, it is largely unknown how transgene expression influences auditory phenotype. We previously observed reduced auditory sensitivity in adult Brn3c:mGFP transgenic zebrafish, which express membrane-bound green fluorescent protein (GFP) in sensory hair cells.

Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity.

Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients.

Effects of Hatchery Rearing on the Structure and Function of Salmonid Mechanosensory Systems.

This paper reviews recent studies on the effects of hatchery rearing on the auditory and lateral line systems of salmonid fishes. Major conclusions are that (1) hatchery-reared juveniles exhibit abnormal lateral line morphology (relative to wild-origin conspecifics), suggesting that the hatchery environment affects lateral line structure, perhaps due to differences in the hydrodynamic conditions of hatcheries versus natural rearing environments, and (2) hatchery-reared salmonids have a high proportion of abnormal otoliths, a condition associated with reduced auditory sensitivity and suggestive of inner ear dysfunction.

Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes.

Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations.

Chemical Ototoxicity of the Fish Inner Ear and Lateral Line.

Hair cell-driven mechanosensory systems are crucial for successful execution of a number of behaviors in fishes, and have emerged as good models for exploring questions relevant to human hearing. This review focuses on ototoxic effects in the inner ear and lateral line system of fishes. We specifically examine studies where chemical ototoxins such as aminoglycoside antibiotics have been employed as tools to disable the lateral line.

Fishy Hearing: A Short Biography of Arthur N. Popper, PhD.

Biologist Dr. Arthur Popper's career spans decades, from his early work on comparative inner ear morphology in fishes to his recent interest in how underwater noise impacts aquatic vertebrates. Along the way Dr.

Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure.

Loss of sensory hair cells from exposure to certain licit drugs (e.g., aminoglycoside antibiotics, platinum-based chemotherapy agents) can result in permanent hearing loss.

The effect of the aquatic contaminants bisphenol-A and PCB-95 on the zebrafish lateral line.

Environmental toxicants such as bisphenol-A (BPA) and polychlorinated biphenyls (PCBs) are prevalent in our water supply, soil, and many food products and can profoundly affect the central nervous system. Both BPA and PCBs can disrupt endocrine signaling, which is important for auditory development and function, but the effect of these toxicants on the auditory periphery is not understood. In this study we investigated the effect of PCB-95 and BPA on lateral line development, function, and regeneration in larval zebrafish.