Protein profile of mouse endolymph suggests a role in controlling cochlear homeostasis.

The cochlea contains two extracellular fluids, perilymph and endolymph. Endolymph exhibits high potential of approximately +80 to +110 mV (depending on species), which sensitizes sensory hair cells. Other properties of this unique fluid remain elusive, owing to its minuscule volume in rodent cochlea.

Biocompatible Core-Shell Microneedle Sensor Filled with Zwitterionic Polymer Hydrogel for Rapid Continuous Transdermal Monitoring.

Microneedle (MN)-based electrochemical biosensors hold promising potential for noninvasive continuous monitoring of interstitial fluid biomarkers. However, challenges, such as instability and biofouling, exist. This study proposes a design employing hollow MN to encapsulate a zwitterionic polymer hydrogel sensing layer with excellent biocompatibility and antifouling properties to address these issues.

Disturbance in the protein landscape of cochlear perilymph in an Alzheimer's disease mouse model.

Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in the initiation and progression of this disease. However, whether the cochlear properties can be influenced by pathological signals associated with dementia remains unclear.

Classification of multiple emotional states from facial expressions in head-fixed mice using a deep learning-based image analysis.

Facial expressions are widely recognized as universal indicators of underlying internal states in most species of animals, thereby presenting as a non-invasive measure for assessing physical and mental conditions. Despite the advancement of artificial intelligence-assisted tools for automated analysis of voluminous facial expression data in human subjects, the corresponding tools for mice still remain limited so far. Considering that mice are the most prevalent model animals for studying human health and diseases, a comprehensive characterization of emotion-dependent patterns of facial expressions in mice could extend our knowledge on the basis of emotions and the related disorders.

A strategy for low-cost portable monitoring of plasma drug concentrations using a sustainable boron-doped-diamond chip.

On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material.

Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice.

An MSM/Ms strain was established using Japanese wild mice, which exhibit resistance to several phenotypes associated with aging, such as obesity, inflammation, and tumorigenesis, compared to common inbred mouse strains. MSM/Ms strain is resistant to age-related hearing loss, and their auditory abilities are sustained for long durations. The age-related hearing loss 3 () locus contributes to age-related hearing in MSM/Ms strain.

A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain.

Oxytocin (OT), a hypothalamic neuropeptide that acts as a neuromodulator in the brain, orchestrates a variety of animal behaviors. However, the relationship between brain OT dynamics and complex animal behaviors remains largely elusive, partly because of the lack of a suitable technique for its real-time recording in vivo. Here, we describe MTRIA, a G-protein-coupled receptor-based green fluorescent OT sensor that has a large dynamic range, suitable affinity, ligand specificity for OT orthologs, minimal effects on downstream signaling and long-term fluorescence stability.

A rapid and simple electrochemical detection of the free drug concentration in human serum using boron-doped diamond electrodes.

Monitoring drug concentration in blood and reflecting this in the dosage are crucial for safe and effective drug treatment. Most drug assays are based on total concentrations of bound and unbound proteins in the serum, although only the unbound concentration causes beneficial and adverse events. Monitoring the unbound concentration alone is expected to provide a means for further optimisation of drug treatment.

Electrochemical properties of the non-excitable tissue stria vascularis of the mammalian cochlea are sensitive to sounds.

Excitable cochlear hair cells convert the mechanical energy of sounds into the electrical signals necessary for neurotransmission. The key process is cellular depolarization via K entry from K -enriched endolymph through hair cells' mechanosensitive channels. Positive 80 mV potential in endolymph accelerates the K entry, thereby sensitizing hearing.

Rapid optical tomographic vibrometry using a swept multi-gigahertz comb.

We propose a rapid tomographic vibrometer technique using an optical comb to measure internal vibrations, transient phenomena, and tomographic distributions in biological tissue and microelectromechanical system devices at high frequencies. This method allows phase-sensitive tomographic measurement in the depth direction at a multi-MHz scan rate using a frequency-modulated broadband electrooptic multi-GHz supercontinuum comb. The frequency spacing was swept instantaneously in time and axisymmetrically about the center wavelength via a dual-drive Mach-Zehnder modulator driven by a variable radio frequency signal.

Analysis of Pharmacokinetics in the Cochlea of the Inner Ear.

Hearing loss affects >5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available.

Real-Time Simultaneous Examination of Drug Kinetics at Two Separate Locations Using Boron-Doped Diamond Microelectrodes.

Methylcobalamin, which is used for the clinical treatment of patients with neuropathy, can have an impact on the sensorineural components associated with the cochlea, and it is possible that the auditory threshold in a certain population of patients with deafness may be recovered. Nonetheless, it remains uncertain whether the action site of methylcobalamin is localized inside or outside the cochlea and which cellular or tissue element is targeted by the drug. In the present work, we developed a method to realize real-time simultaneous examination of the drug kinetics in two separate locations using boron-doped diamond microelectrodes.

Characterisation of the static offset in the travelling wave in the cochlear basal turn.

In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset.

An electrochemical aptamer-based sensor prepared by utilizing the strong interaction between a DNA aptamer and diamond.

Stable and continuous biosensing of electroactive species in vivo has been achieved by using boron-doped diamond (BDD) electrodes owing to their outstanding electrochemical properties. However, the present problem in biosensing using BDD electrodes is how to specifically measure/detect the target molecules, including electrochemically inactive species. A possible solution is to fabricate an electrochemical aptamer-based (E-AB) sensor using a BDD electrode.

tomographic visualization of intracochlear vibration using a supercontinuum multifrequency-swept optical coherence microscope.

This study combined a previously developed optical system with two additional key elements: a supercontinuum light source characterized by high output power and an analytical technique that effectively extracts interference signals required for improving the detection limit of vibration amplitude. Our system visualized 3D tomographic images and nanometer scale vibrations in the cochlear sensory epithelium of a live guinea pig. The transverse- and axial-depth resolution was 3.

[Development of in vivo drug sensing system with needle-type diamond microelectrode].

Continuous and real-time measurement of local concentrations of systemically administered drugs in vivo must be crucial for pharmacological studies. Nevertheless, conventional methods require considerable samples quantity and have poor sampling rates. Additionally, they cannot determine how drug kinetics correlates with target function over time.

Integrative and theoretical research on the architecture of a biological system and its disorder.

An organism stems from assemblies of a variety of cells and proteins. This complex system serves as a unit, and it exhibits highly sophisticated functions in response to exogenous stimuli that change over time. The complete sequencing of the entire human genome has allowed researchers to address the enigmas of life and disease at the gene- or molecular-based level.

Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea.

Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities. N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues. In several organs, profiles of N-glycans have been determined by comprehensive analyses.

Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice.

Identification of the causal effects of specific proteins on recurrent and partially reversible hearing loss has been difficult because of the lack of an animal model that provides reversible gene knockdown. We have developed the transgenic mouse line Actin-tTS::Nkcc1 for manipulatable expression of the cochlear K circulation protein, NKCC1. Nkcc1 transcription was blocked by the binding of a tetracycline-dependent transcriptional silencer to the tetracycline operator sequences inserted upstream of the Nkcc1 translation initiation site.

Hearing Loss Controlled by Optogenetic Stimulation of Nonexcitable Nonglial Cells in the Cochlea of the Inner Ear.

Light-gated ion channels and transporters have been applied to a broad array of excitable cells including neurons, cardiac myocytes, skeletal muscle cells and pancreatic β-cells in an organism to clarify their physiological and pathological roles. Nonetheless, among nonexcitable cells, only glial cells have been studied by this approach. Here, by optogenetic stimulation of a different nonexcitable cell type in the cochlea of the inner ear, we induce and control hearing loss.

Erratum to: An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution.

The article An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution, written by Hiroshi Hibino, Madoka Takai, Hidenori Noguchi, Seishiro Sawamura, Yasufumi Takahashi, Hideki Sakai and Hitoshi Shiku, was originally published Online First without open access.

Computer modeling defines the system driving a constant current crucial for homeostasis in the mammalian cochlea by integrating unique ion transports.

The cochlear lateral wall-an epithelial-like tissue comprising inner and outer layers-maintains +80 mV in endolymph. This endocochlear potential supports hearing and represents the sum of all membrane potentials across apical and basolateral surfaces of both layers. The apical surfaces are governed by K equilibrium potentials.

A microsensing system for the in vivo real-time detection of local drug kinetics.

Real-time recording of the kinetics of systemically administered drugs in in vivo microenvironments may accelerate the development of effective medical therapies. However, conventional methods require considerable analyte quantities, have low sampling rates and do not address how drug kinetics correlate with target function over time. Here, we describe the development and application of a drug-sensing system consisting of a glass microelectrode and a microsensor composed of boron-doped diamond with a tip of around 40 μm in diameter.