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The Journal of General Physiology Jun 2024In this Viewpoint, Holt, Fettiplace, and Müller weigh the evidence supporting a role for PIEZO and TMC channels in mechanosensory transduction in inner ear hair cells.
In this Viewpoint, Holt, Fettiplace, and Müller weigh the evidence supporting a role for PIEZO and TMC channels in mechanosensory transduction in inner ear hair cells.
Topics: Hair Cells, Auditory; Animals; Humans; Mechanotransduction, Cellular; Ion Channels
PubMed: 38727631
DOI: 10.1085/jgp.202413585 -
Cells Apr 2024In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae...
In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae may be a therapeutic target for hearing regeneration. The ubiquitin proteasome system plays an important role in cochlear development and maintenance. In this study, we investigated the role of ubiquitin C-terminal hydrolase L1 (UCHL1) in the process of the transdifferentiation of auditory supporting cells (SCs) into hair cells (HCs). The expression of UCHL1 gradually decreased as HCs developed and was restricted to inner pillar cells and third-row Deiters' cells between P2 and P7, suggesting that UCHL1-expressing cells are similar to the cells with Lgr5-positive progenitors. UCHL1 expression was decreased even under conditions in which supernumerary HCs were generated with a γ-secretase inhibitor and Wnt agonist. Moreover, the inhibition of UCHL1 by LDN-57444 led to an increase in HC numbers. Mechanistically, LDN-57444 increased mTOR complex 1 activity and allowed SCs to transdifferentiate into HCs. The suppression of UCHL1 induces the transdifferentiation of auditory SCs and progenitors into HCs by regulating the mTOR pathway.
Topics: Animals; Cell Transdifferentiation; Hair Cells, Auditory; Indoles; Labyrinth Supporting Cells; Oximes; Signal Transduction; TOR Serine-Threonine Kinases; Ubiquitin Thiolesterase; Rats
PubMed: 38727276
DOI: 10.3390/cells13090737 -
The Journal of Pharmacology and... May 2024Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal...
Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal chemoreceptors and mechanoreceptors and are involved in various rectal hypersensitivity disorders with common features of colorectal overactivity. These stimulatory properties of TRPV1 receptors on colorectal function suggested that brief stimulation of TRPV1 might provide a means of pharmacologically activating the colorectum to induce defecation in patients with an "unresponsive" colorectum. The current studies explored the basic features of TRPV1 receptor-induced contractions of the colorectum in anesthetized rats with and without acute spinal cord injury (aSCI). Cumulative concentration-response curves to intrarectal (IR) capsaicin (CAP) solutions (0.003% to 3.0%) were performed in anesthetized aSCI and spinal intact rats. CAP produced an "inverted U", cumulative concentration-response curve with a threshold for inducing colorectal contractions at 0.01% and a peak response at 0.1% and slight decreases in responses up to 3%. Decreases in responses with concentrations > 0.1% are due to a rapid desensitization (i.e. 30 min) of TRPV1 receptors to each successive dose. Desensitization appeared fully recovered within 24 hours in spinal intact rats. Colorectal contractions were completely blocked by atropine, indicating a reflexogenic activation of parasympathetic neurons, and responses were completely unaffected by a neurokinin 2 receptor antagonist, indicating that release of neurokinin A (NKA) from afferent terminals and subsequent direct contractions of the smooth muscle was not involved. IR administration of 3 other TRPV1 receptor agonists produced similar results as CAP. Individuals with spinal cord injury often lose control of defecation. Time consuming and inconvenient bowel programs using digital stimulation of the rectum and manual extraction of stool are used to empty the bowel. We show that intrarectal administration of the TRPV1 receptor agonist, capsaicin, can induce rapid onset, short duration colorectal contractions capable of inducing defecation in spinal cord injured and intact rats. Therefore, TRPV1 agonists show promise as a potential therapeutics to induce defecation in individuals with neurogenic bowel.
PubMed: 38719479
DOI: 10.1124/jpet.123.001989 -
Hearing Research Jun 2024Cisplatin, a highly effective chemotherapeutic drug for various human cancers, induces irreversible sensorineural hearing loss as a side effect. Currently there are no...
Cisplatin, a highly effective chemotherapeutic drug for various human cancers, induces irreversible sensorineural hearing loss as a side effect. Currently there are no highly effective clinical strategies for the prevention of cisplatin-induced ototoxicity. Previous studies have indicated that short-term cisplatin ototoxicity primarily affects the outer hair cells of the cochlea. Therefore, preventing the entry of cisplatin into hair cells may be a promising strategy to prevent cisplatin ototoxicity. This study aimed to investigate the entry route of cisplatin into mouse cochlear hair cells. The competitive inhibitor of organic cation transporter 2 (OCT2), cimetidine, and the sensory mechanoelectrical transduction (MET) channel blocker benzamil, demonstrated a protective effect against cisplatin toxicity in hair cells in cochlear explants. Sensory MET-deficient hair cells explanted from Tmc1;Tmc2 mice were resistant to cisplatin toxicity. Cimetidine showed an additive protective effect against cisplatin toxicity in sensory MET-deficient hair cells. However, in the apical turn, cimetidine, benzamil, or genetic ablation of sensory MET channels showed limited protective effects, implying the presence of other entry routes for cisplatin to enter the hair cells in the apical turn. Systemic administration of cimetidine failed to protect cochlear hair cells from ototoxicity caused by systemically administered cisplatin. Notably, outer hair cells in MET-deficient mice exhibited no apparent deterioration after systemic administration of cisplatin, whereas the outer hair cells in wild-type mice showed remarkable deterioration. The susceptibility of mouse cochlear hair cells to cisplatin ototoxicity largely depends on the sensory MET channel both ex vivo and in vivo. This result justifies the development of new pharmaceuticals, such as a specific antagonists for sensory MET channels or custom-designed cisplatin analogs which are impermeable to sensory MET channels.
Topics: Cisplatin; Animals; Ototoxicity; Mechanotransduction, Cellular; Organic Cation Transporter 2; Cimetidine; Antineoplastic Agents; Hair Cells, Auditory; Hair Cells, Auditory, Outer; Mice, Inbred C57BL; Mice; Membrane Proteins
PubMed: 38718672
DOI: 10.1016/j.heares.2024.109013 -
Integrative Organismal Biology (Oxford,... 2024Flight control requires active sensory feedback, and insects have many sensors that help them estimate their current locomotor state, including campaniform sensilla...
Flight control requires active sensory feedback, and insects have many sensors that help them estimate their current locomotor state, including campaniform sensilla (CS), which are mechanoreceptors that sense strain resulting from deformation of the cuticle. CS on the wing detect bending and torsional forces encountered during flight, providing input to the flight feedback control system. During flight, wings experience complex spatio-temporal strain patterns. Because CS detect only local strain, their placement on the wing is presumably critical for determining the overall representation of wing deformation; however, how these sensilla are distributed across wings is largely unknown. Here, we test the hypothesis that CS are found in stereotyped locations across individuals of , a hawkmoth. We found that although CS are consistently found on the same veins or in the same regions of the wings, their total number and distribution can vary extensively. This suggests that there is some robustness to variation in sensory feedback in the insect flight control system. The regions where CS are consistently found provide clues to their functional roles, although some patterns might be reflective of developmental processes. Collectively, our results on intraspecific variation in CS placement on insect wings will help reshape our thinking on the utility of mechanosensory feedback for insect flight control and guide further experimental and comparative studies.
PubMed: 38715720
DOI: 10.1093/iob/obae007 -
BioRxiv : the Preprint Server For... Apr 2024Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological...
Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.
PubMed: 38712022
DOI: 10.1101/2024.02.20.581208 -
Hearing Research Jun 2024Understanding the complex pathologies associated with hearing loss is a significant motivation for conducting inner ear research. Lifelong exposure to loud noise,... (Review)
Review
Understanding the complex pathologies associated with hearing loss is a significant motivation for conducting inner ear research. Lifelong exposure to loud noise, ototoxic drugs, genetic diversity, sex, and aging collectively contribute to human hearing loss. Replicating this pathology in research animals is challenging because hearing impairment has varied causes and different manifestations. A central aspect, however, is the loss of sensory hair cells and the inability of the mammalian cochlea to replace them. Researching therapeutic strategies to rekindle regenerative cochlear capacity, therefore, requires the generation of animal models in which cochlear hair cells are eliminated. This review discusses different approaches to ablate cochlear hair cells in adult mice. We inventoried the cochlear cyto- and histo-pathology caused by acoustic overstimulation, systemic and locally applied drugs, and various genetic tools. The focus is not to prescribe a perfect damage model but to highlight the limitations and advantages of existing approaches and identify areas for further refinement of damage models for use in regenerative studies.
Topics: Animals; Hair Cells, Auditory; Disease Models, Animal; Regeneration; Mice; Cochlea; Humans; Hearing; Hearing Loss, Noise-Induced; Hearing Loss; Acoustic Stimulation
PubMed: 38703432
DOI: 10.1016/j.heares.2024.109021 -
Advanced Materials (Deerfield Beach,... May 2024In the era of artificial intelligence (AI), there is a growing interest in replicating human sensory perception. Selective and sensitive bio-inspired sensory receptors... (Review)
Review
In the era of artificial intelligence (AI), there is a growing interest in replicating human sensory perception. Selective and sensitive bio-inspired sensory receptors with synaptic plasticity have recently gained significant attention in developing energy-efficient AI perception. Various bio-inspired sensory receptors and their applications in AI perception are reviewed here. The critical challenges for the future development of bio-inspired sensory receptors are outlined, emphasizing the need for innovative solutions to overcome hurdles in sensor design, integration, and scalability. AI perception can revolutionize various fields, including human-machine interaction, autonomous systems, medical diagnostics, environmental monitoring, industrial optimization, and assistive technologies. As advancements in bio-inspired sensing continue to accelerate, the promise of creating more intelligent and adaptive AI systems becomes increasingly attainable, marking a significant step forward in the evolution of human-like sensory perception.
PubMed: 38699932
DOI: 10.1002/adma.202403150 -
Nature Communications May 2024
PubMed: 38693221
DOI: 10.1038/s41467-024-48095-6 -
Journal of Hand Therapy : Official... 2024Taping stimulates the mechanoreceptors, increases sensory information to the central nervous system, and improves sensorimotor synchronization, resulting in improved... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Taping stimulates the mechanoreceptors, increases sensory information to the central nervous system, and improves sensorimotor synchronization, resulting in improved motor control. However, the efficacy of taping on elbow proprioception is not clear.
PURPOSE
This study aimed to evaluate the immediate effects of taping on elbow proprioception in healthy individuals.
STUDY DESIGN
This study was a two-arm, parallel-group, randomized, controlled, single-blinded study with a sham application.
METHODS
Fifty six healthy adults were randomized 1:1 to kinesio taping (n = 27) or sham taping (n = 29). Active joint position sense error (JPSE) was used to quantify proprioception using a universal goniometer at three-time points: baseline (BS), immediately after taping (IA), and 30 minutes after taping (30MA), with the tape still in place at 70° and 110° of elbow flexion. Participants were blinded to group assignments. The Friedman analysis assessed differences between evaluations within groups, and the Mann-Whitney U test determined differences between groups.
RESULTS
The study was completed with 56 participants and there were no dropouts. No skin reaction or adverse effect was observed in the participants and no test trial was excluded. The baseline scores of the groups were similar (p > 0.05). A significant difference was detected in the study group after kinesio taping at 70° (MD = -1.22; CI = (-2.33: -0.10; p < 0.005; d = 0.653) and 110° of elbow flexion (MD = -1.34; CI = 2,47: -0,21; p < 0.005; d = 0.73). This statistically significant difference was observed even at the 30MA evaluations at 70° (p < 0.05). Also, there was a statistically insignificant tendency to decrease in JPSE of both groups at both degrees following taping.
CONCLUSIONS
Elbow proprioception may be enhanced by kinesio taping, and this effect could last up to 30 minutes at 70° of elbow flexion. In contrast, sham taping did not produce such an improvement. Based on the differences in JPSE, kinesio taping proved more effective and had a longer-lasting impact than the sham application. The statistically insignificant tendency to decrease in JPSE may indicate that the 30-minute application period is inadequate to create a statistically significant effect on elbow proprioception. Longer usage periods can better reveal the effects of orthoses on proprioception.
Topics: Humans; Proprioception; Single-Blind Method; Male; Female; Athletic Tape; Adult; Elbow Joint; Young Adult; Healthy Volunteers; Range of Motion, Articular
PubMed: 38692994
DOI: 10.1016/j.jht.2024.02.014