Biology subjects

Jeng, J.-Y.

Publications and source records attributed to Jeng, J.-Y..

5 recordsLinked to original sources

bioRxiv2025

Aging Alters Hair Cell Physiological Properties in Mice with Late-Onset Age-Related Hearing Loss.

Cochlear hair cells convert sound stimuli into electrical signals. Age-related hearing loss (ARHL) is characterized by the progressive reduction of these hair cells and their synapses, but the underlying mechanisms remain poorly understood. In this study, we tested the hypothesis that hair cell function declines with age in CBA/CaJ mice, a strain known for its very slow ARHL progression. We found that hair cell size began to decrease from 10 months of age, before hearing loss was detectable. This structural change was associated with a significant decrease in the total current response and a distinct reduction in the expression of large conductance calcium-activated potassium (BK) channel currents (IK,f). However, the magnitude of the mechanoelectrical transducer (MET) currents at the hair cell stereociliary bundles remained unaffected. This observation challenges the common conception that stereocilia are the most fragile component of sensory cells in aging. Our results provide clear evidence of an early decline in hair cell function with age, which precedes measurable hearing loss, suggesting that these cellular deficits define a distinct pathological route to ARHL in the CBA/CaJ mouse model.

physiology↗

bioRxiv2024

Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice

Tight regulation of Ca2+ is crucial for the function of cochlear outer hair cells (OHCs). Dysregulation of Ca2+ homeostasis in OHCs is associated with impaired hearing and contributes to increased vulnerability to insults such as noise exposure. Ca2+ signaling in developing OHCs is modulated by oncomodulin (OCM), an EF-hand calcium-binding protein. Here, we investigated whether the lack of OCM disrupts the control of intracellular Ca2+ in mature OHCs, and influences vulnerability to acoustic injury. Using young adult CBA/CaJ mice, we found that OHCs from Ocm-knockout (Ocm-/-) mice showed normal biophysical profiles, electromotile responses, and synaptic innervation compared to littermate controls. Moderate noise exposure (95 dB SPL, 2 hrs) caused temporary threshold shifts in Ocm+/+ and Ocm-/- mice. However, while Ocm+/+ fully recovered thresholds 2 weeks after noise exposure, Ocm-/- mice showed permanent threshold shifts. Additionally, Ocm-/- mice had auditory brainstem responses with highly variable latencies and amplitudes both before and after noise exposure compared to Ocm+/+ mice. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in Ocm+/+ and Ocm-/- OHCs, we found that prolonged noise exposure (95 dB SPL, 9 hrs) significantly increased GCaMP6s fluorescence, ATP-induced Ca2+ signaling and also caused greater threshold shifts in Ocm-/- compared to Ocm+/+ OHCs. However, prolonged noise exposure had no significant change in the number of presynaptic OHC ribbons in either Ocm+/+ or Ocm-/- mice. We assessed whether the ATP-induced responses were due to changes in P2X2 receptor expression. Prior to noise exposure, P2X2 expression was higher in the cochlea of Ocm-/- mice compared to Ocm+/+ mice. Following prolonged noise, P2X2 receptors were upregulated in the cochlea of Ocm+/+ but not in the Ocm-/- mice, which retained their pre-noise expression level. We propose that the lack of OCM increases susceptibility to cochlear pathology and that purinergic signaling and dysregulation of cytosolic Ca2+ homeostasis likely contribute to early onset hearing loss in the Ocm-/- mice.

neuroscience↗

bioRxiv2022

Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.

In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), -parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and in transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.

developmental biology↗

bioRxiv2020

CyDAP-A fluorescent probe for cytosolic dopamine detection

Dopamine (DA) is an essential neurotransmitter modulating motor and cognitive functions. Several neurological disorders, including Parkinsons disease (PD) and drug addiction, are the result of DA system dysfunction; however, it remains incomplete understood of why DA neuron is selectively more vulnerable than other neurons. Here we utilize the spectral feature of human MAO B (monoamine oxidase B) to design a genetic-amenable, GFP-based fluorescent probe CyDAP. Upon genetic and pharmacological manipulations to elevate the cytosolic DA levels in cells and Drosophila models, CyDAP shows enhanced GFP emission, suggesting this probe is feasible for DA detection. Furthermore, we observe that expressing human -Synuclein in Drosophila elicited GFP emission from CyDAP, suggesting a link between cytosolic DA imbalance and regional vulnerability in PD context. Importantly, CyDAP can detect the change of cytosolic DA in live Drosophila brains, as demonstrated by time-lapse and the 4D light-sheet confocal recording. CyDAP may serve as a tool for evaluating metabolic deregulation of DA in brain models of PD and other DA system-related psychiatric disorders.

neuroscience↗

bioRxiv2018

Spontaneous and coordinated Ca2+ activity of cochlear sensory and non-sensory cells drives the maturation of OHC afferent innervation

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca2+ spikes during a narrow period of immature development. Simultaneously, waves of Ca2+ activity in the non-sensory greater epithelial ridge act, via ATP-induced activation of P2X receptors, to synchronize OHC firing, resulting in the refinement of their afferent innervation. In the absence of connexin channels Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity in OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells.

neuroscience↗