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1.
Elife ; 122023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607222

RESUMO

Afferents of peripheral mechanoreceptors innervate the skin of vertebrates, where they detect physical touch via mechanically gated ion channels (mechanotransducers). While the afferent terminal is generally understood to be the primary site of mechanotransduction, the functional properties of mechanically activated (MA) ionic current generated by mechanotransducers at this location remain obscure. Until now, direct evidence of MA current and mechanically induced action potentials in the mechanoreceptor terminal has not been obtained. Here, we report patch-clamp recordings from the afferent terminal innervating Grandry (Meissner) corpuscles in the bill skin of a tactile specialist duck. We show that mechanical stimulation evokes MA current in the afferent with fast kinetics of activation and inactivation during the dynamic phases of the mechanical stimulus. These responses trigger rapidly adapting firing in the afferent detected at the terminal and in the afferent fiber outside of the corpuscle. Our findings elucidate the initial electrogenic events of touch detection in the mechanoreceptor nerve terminal.


Assuntos
Percepção do Tato , Tato , Animais , Tato/fisiologia , Mecanotransdução Celular/fisiologia , Mecanorreceptores/fisiologia , Pele/inervação
2.
Mol Pain ; 19: 17448069221148958, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36526445

RESUMO

The role of Aß-afferents in somatosensory function is often oversimplified as low threshold mechanoreceptors (LTMRs) with large omission of Aß-afferent involvement in nociception. Recently, we have characterized Aß-afferent neurons which have large diameter somas in the trigeminal ganglion (TG) and classified them into non-nociceptive and nociceptive-like TG afferent neurons based on their electrophysiological properties. Here, we extend our previous observations to further characterize electrophysiological properties of trigeminal Aß-afferent neurons and investigate their mechanical and chemical sensitivity by patch-clamp recordings from large-diameter TG neurons in ex vivo TG preparations of adult male and female rats. Based on cluster analysis of electrophysiological properties, trigeminal Aß-afferent neurons can be classified into five discrete types (type I, IIa, IIb, IIIa, and IIIb), which responded differentially to mechanical stimulation and sensory mediators including serotonin (5-HT), acetylcholine (ACh) and adenosine triphosphate (ATP). Notably, type I neuron action potential (AP) was small in amplitude, width was narrow in duration, and peak dV/dt repolarization was great with no deflection observed, whereas discretely graded differences were observed for type IIa, IIb, IIIa, and IIIb, as AP increased in amplitude, width broadened in duration, and peak dV/dt repolarization reduced with the emergence of increasing deflection. Type I, IIa, and IIb neurons were mostly mechanically sensitive, displaying robust and rapidly adapting mechanically activated current (IMA) in response to membrane displacement, while IIIa and IIIb, conversely, were almost all mechanically insensitive. Interestingly, mechanical insensitivity coincided with increased sensitivity to 5-HT and ACh. Together, type I, IIa and IIb display features of LTMR Aß-afferent neurons while type IIIa and type IIIb show properties of nociceptive Aß-afferent neurons.


Assuntos
Neurônios Aferentes , Serotonina , Ratos , Masculino , Feminino , Animais , Neurônios Aferentes/fisiologia , Nociceptores/fisiologia , Mecanorreceptores , Neurônios , Potenciais de Ação/fisiologia , Gânglio Trigeminal
3.
J Physiol ; 601(2): 275-285, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36510697

RESUMO

Muscle spindles, one of the two main classes of proprioceptors together with Golgi tendon organs, are sensory structures that keep the central nervous system updated about the position and movement of body parts. Although they were discovered more than 150 years ago, their function during movement is not yet fully understood. Here, we summarize the morphology and known functions of muscle spindles, with a particular focus on locomotion. Although certain properties such as the sensitivity to dynamic and static muscle stretch are long known, recent advances in molecular biology have allowed the characterization of the molecular mechanisms for signal transduction in muscle spindles. Building upon classic literature showing that a lack of sensory feedback is deleterious to locomotion, we bring to the discussion more recent findings that support a pivotal role of muscle spindles in maintaining murine and human locomotor robustness, defined as the ability to cope with perturbations. Yet, more research is needed to expand the existing mechanistic understanding of how muscle spindles contribute to the production of robust, functional locomotion in real world settings. Future investigations should focus on combining different animal models to identify, in health and disease, those peripheral, spinal and brain proprioceptive structures involved in the fine tuning of motor control when locomotion happens in challenging conditions.


Assuntos
Mecanorreceptores , Fusos Musculares , Camundongos , Humanos , Animais , Fusos Musculares/fisiologia , Mecanorreceptores/fisiologia , Propriocepção/fisiologia , Locomoção/fisiologia , Coluna Vertebral , Músculo Esquelético/fisiologia
4.
PLoS Comput Biol ; 18(12): e1010763, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36477028

RESUMO

Sensory information is conveyed by populations of neurons, and coding strategies cannot always be deduced when considering individual neurons. Moreover, information coding depends on the number of neurons available and on the composition of the population when multiple classes with different response properties are available. Here, we study population coding in human tactile afferents by employing a recently developed simulator of mechanoreceptor firing activity. First, we highlight the interplay of afferents within each class. We demonstrate that the optimal afferent density to convey maximal information depends on both the tactile feature under consideration and the afferent class. Second, we find that information is spread across different classes for all tactile features and that each class encodes both redundant and complementary information with respect to the other afferent classes. Specifically, combining information from multiple afferent classes improves information transmission and is often more efficient than increasing the density of afferents from the same class. Finally, we examine the importance of temporal and spatial contributions, respectively, to the joint spatiotemporal code. On average, destroying temporal information is more destructive than removing spatial information, but the importance of either depends on the stimulus feature analyzed. Overall, our results suggest that both optimal afferent innervation densities and the composition of the population depend in complex ways on the tactile features in question, potentially accounting for the variety in which tactile peripheral populations are assembled in different regions across the body.


Assuntos
Mecanorreceptores , Tato , Humanos , Potenciais de Ação/fisiologia , Tato/fisiologia , Mecanorreceptores/fisiologia , Neurônios , Neurônios Aferentes/fisiologia
5.
Cells ; 11(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36497085

RESUMO

Merkel cells (MCs) are rare multimodal epidermal sensory cells. Due to their interactions with slowly adapting type 1 (SA1) Aß low-threshold mechanoreceptor (Aß-LTMRs) afferents neurons to form Merkel complexes, they are considered to be part of the main tactile terminal organ involved in the light touch sensation. This function has been explored over time by ex vivo, in vivo, in vitro, and in silico approaches. Ex vivo studies have made it possible to characterize the topography, morphology, and cellular environment of these cells. The interactions of MCs with surrounding cells continue to be studied by ex vivo but also in vitro approaches. Indeed, in vitro models have improved the understanding of communication of MCs with other cells present in the skin at the cellular and molecular levels. As for in vivo methods, the sensory role of MC complexes can be demonstrated by observing physiological or pathological behavior after genetic modification in mouse models. In silico models are emerging and aim to elucidate the sensory coding mechanisms of these complexes. The different methods to study MC complexes presented in this review may allow the investigation of their involvement in other physiological and pathophysiological mechanisms, despite the difficulties in exploring these cells, in particular due to their rarity.


Assuntos
Células de Merkel , Neurônios Aferentes , Camundongos , Animais , Células de Merkel/fisiologia , Mecanorreceptores , Pele
6.
Sci Rep ; 12(1): 21690, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36522364

RESUMO

The sense of touch plays a fundamental role in enabling us to interact with our surrounding environment. Indeed, the presence of tactile feedback in prostheses greatly assists amputees in doing daily tasks. In this line, the present study proposes an integration of artificial tactile and proprioception receptors for texture discrimination under varying scanning speeds. Here, we fabricated a soft biomimetic fingertip including an 8 × 8 array tactile sensor and a piezoelectric sensor to mimic Merkel, Meissner, and Pacinian mechanoreceptors in glabrous skin, respectively. A hydro-elastomer sensor was fabricated as an artificial proprioception sensor (muscle spindles) to assess the instantaneous speed of the biomimetic fingertip. In this study, we investigated the concept of the complex receptive field of RA-I and SA-I afferents for naturalistic textures. Next, to evaluate the synergy between the mechanoreceptors and muscle spindle afferents, ten naturalistic textures were manipulated by a soft biomimetic fingertip at six different speeds. The sensors' outputs were converted into neuromorphic spike trains to mimic the firing pattern of biological mechanoreceptors. These spike responses are then analyzed using machine learning classifiers and neural coding paradigms to explore the multi-sensory integration in real experiments. This synergy between muscle spindle and mechanoreceptors in the proposed neuromorphic system represents a generalized texture discrimination scheme and interestingly irrespective of the scanning speed.


Assuntos
Percepção do Tato , Tato , Tato/fisiologia , Mecanorreceptores/fisiologia , Pele , Propriocepção
7.
eNeuro ; 9(6)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36376066

RESUMO

Angular tuning is preferential sensory response to a directional stimulus and is observed in the whisker tactile system. In whisker hair follicles, there are at least three types of low threshold mechanoreceptors (LTMRs): rapidly adapting (RA), slowly adapting type 1 (SA1), and slowly adapting type 2 (SA2). These LTMRs display angular tuning but their properties remain incompletely studied. Here, we used isolated rat whisker hair follicles and pressure-clamped single-fiber recordings to study angular tuning of these LTMRs. Angular tuning was determined with impulses elicited by ramp-and-hold deflection of whisker hair in 24 directions each at 15° for a total of 360°. We show that RA display impulses during ramp-up, both ramp-up and ramp-down, or ramp-down dynamic phases. Both SA1 and SA2 respond to angular stimuli with slowly adapting impulses in most angles. However, SA1 and SA2 show rapidly adapting responses in other angles. All the three types of LTMRs display strong angular tuning, and there is no significant difference in angular tuning index among them. Population wise, the majority of SA1 are tuned in the caudal direction, a large part of SA2 is tuned in the rostral direction, and RAs are tuned in multiple directions. In the angles showing strong tuning, the three LTMRs respond to increased stimulation amplitudes with increased impulse numbers in a hyperbola relationship, and the responsiveness based on impulse numbers is SA2 > SA1 > RA. Our findings provide new information on angular tuning properties of LTMRs in whisker hair follicles and help to understand directional encoding.


Assuntos
Folículo Piloso , Vibrissas , Ratos , Animais , Folículo Piloso/fisiologia , Mecanorreceptores , Cabelo , Tato
8.
Cell ; 185(24): 4541-4559.e23, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36334588

RESUMO

The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale in vivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles. Genetic disruption of DH feedforward or feedback inhibitory motifs, comprised of interneurons with distinct mechanical response profiles, revealed an extensively interconnected DH network that enables dynamic, flexible tuning of postsynaptic dorsal column (PSDC) output neurons and dictates how neurons in the primary somatosensory cortex respond to touch. Thus, mechanoreceptor subtype convergence and non-linear transformations at the earliest stage of the somatosensory hierarchy shape how touch of the skin is represented in the brain.


Assuntos
Mecanorreceptores , Corno Dorsal da Medula Espinal , Animais , Camundongos , Tato/fisiologia , Interneurônios , Encéfalo , Medula Espinal
9.
Sci Rep ; 12(1): 20172, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36424494

RESUMO

Insect antennae are astonishingly versatile and have multiple sensory modalities. Audition, detection of airflow, and graviception are combined in the antennal chordotonal organs. The miniaturization of these complex multisensory organs has never been investigated. Here we present a comprehensive study of the structure and scaling of the antennal chordotonal organs of the extremely miniaturized parasitoid wasp Megaphragma viggianii based on 3D electron microscopy. Johnston's organ of M. viggianii consists of 19 amphinematic scolopidia (95 cells); the central organ consists of five scolopidia (20 cells). Plesiomorphic composition includes one accessory cell per scolopidium, but in M. viggianii this ratio is only 0.3. Scolopale rods in Johnston's organ have a unique structure. Allometric analyses demonstrate the effects of scaling on the antennal chordotonal organs in insects. Our results not only shed light on the universal principles of miniaturization of sense organs, but also provide context for future interpretation of the M. viggianii connectome.


Assuntos
Antenas de Artrópodes , Mecanorreceptores , Animais , Mecanorreceptores/ultraestrutura , Órgãos dos Sentidos/ultraestrutura , Microscopia Eletrônica , Insetos
10.
Elife ; 112022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36314774

RESUMO

Fast-adapting type 1 (FA-1) and slow-adapting type 1 (SA-1) first-order neurons in the human tactile system have distal axons that branch in the skin and form many transduction sites, yielding receptive fields with many highly sensitive zones or 'subfields.' We previously demonstrated that this arrangement allows FA-1 and SA-1 neurons to signal the geometric features of touched objects, specifically the orientation of raised edges scanned with the fingertips. Here, we show that such signaling operates for fine edge orientation differences (5-20°) and is stable across a broad range of scanning speeds (15-180 mm/s); that is, under conditions relevant for real-world hand use. We found that both FA-1 and SA-1 neurons weakly signal fine edge orientation differences via the intensity of their spiking responses and only when considering a single scanning speed. Both neuron types showed much stronger edge orientation signaling in the sequential structure of the evoked spike trains, and FA-1 neurons performed better than SA-1 neurons. Represented in the spatial domain, the sequential structure was strikingly invariant across scanning speeds, especially those naturally used in tactile spatial discrimination tasks. This speed invariance suggests that neurons' responses are structured via sequential stimulation of their subfields and thus links this capacity to their terminal organization in the skin. Indeed, the spatial precision of elicited action potentials rationally matched spatial acuity of subfield arrangements, which corresponds to a spatial period similar to the dimensions of individual fingertip ridges.


Assuntos
Percepção do Tato , Tato , Humanos , Tato/fisiologia , Potenciais de Ação/fisiologia , Neurônios/fisiologia , Dedos/fisiologia , Mecanorreceptores/fisiologia
11.
Physiol Rep ; 10(20): e15479, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36259120

RESUMO

In humans, plantar cutaneous mechanoreceptors provide critical input signals for postural control during walking and running. Because these receptors are located within the dermis, the mechanical properties of the overlying epidermis likely affect the transmission of external stimuli. Epidermal layers are highly adaptable and can form hard and thick protective calluses, but their effects on plantar sensitivity are currently disputed. Some research has shown no effect of epidermal properties on sensitivity to vibrations, whereas other research suggests that vibration and touch sensitivity diminishes with a thicker and harder epidermis. To address this conflict, we conducted an intervention study where 26 participants underwent a callus abrasion while an age-matched control group (n = 16) received no treatment. Skin hardness and thickness as well as vibration perception thresholds and touch sensitivity thresholds were collected before and after the intervention. The Callus abrasion significantly decreased skin properties. The intervention group exhibited no change in vibration sensitivity but had significantly better touch sensitivity. We argue that touch sensitivity was impeded by calluses because hard skin disperses the monofilament's standardized pressure used to stimulate the mechanoreceptors over a larger area, decreasing indentation depth and therefore stimulus intensity. However, vibration sensitivity was unaffected because the vibrating probe was adjusted to reach specific indentation depths, and thus stimulus intensity was not affected by skin properties. Since objects underfoot necessarily indent plantar skin during weight-bearing, calluses should not affect mechanosensation during standing, walking, or running.


Assuntos
, Tato , Humanos , Mecanorreceptores , Pele , Vibração/efeitos adversos
12.
J Gen Physiol ; 154(12)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36256908

RESUMO

The membrane protein TMEM150C has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here, we examined whether expression of TMEM150C in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch, and substrate deflection, we could not evoke mechanosensitive currents in cells expressing TMEM150C. We next asked if TMEM150C is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a CRISPR/Cas9 strategy, we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c-/- mice completely lack TMEM150C protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c-/- mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c-/- mice. Since it has been claimed that TMEM150C is required for normal proprioceptor function, we made a quantitative analysis of locomotion in Tmem150c-/- mice. Here again, we found no indication that there was altered gait in Tmem150c-/- mice compared to wild-type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150C function in vivo are problematic. Furthermore, we could find no evidence that TMEM150C forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons.


Assuntos
Gânglios Espinais , Mecanotransdução Celular , Camundongos , Animais , Mecanotransdução Celular/fisiologia , Gânglios Espinais/metabolismo , Mecanorreceptores/metabolismo , Células Receptoras Sensoriais/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo
13.
Proc Natl Acad Sci U S A ; 119(43): e2210421119, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36252008

RESUMO

Low-threshold mechanoreceptors (LTMRs) and their cutaneous end organs convert light mechanical forces acting on the skin into electrical signals that propagate to the central nervous system. In mouse hairy skin, hair follicle-associated longitudinal lanceolate complexes, which are end organs comprising LTMR axonal endings that intimately associate with terminal Schwann cell (TSC) processes, mediate LTMR responses to hair deflection and skin indentation. Here, we characterized developmental steps leading to the formation of Aß rapidly adapting (RA)-LTMR and Aδ-LTMR lanceolate complexes. During early postnatal development, Aß RA-LTMRs and Aδ-LTMRs extend and prune cutaneous axonal branches in close association with nascent TSC processes. Netrin-G1 is expressed in these developing Aß RA-LTMR and Aδ-LTMR lanceolate endings, and Ntng1 ablation experiments indicate that Netrin-G1 functions in sensory neurons to promote lanceolate ending elaboration around hair follicles. The Netrin-G ligand (NGL-1), encoded by Lrrc4c, is expressed in TSCs, and ablation of Lrrc4c partially phenocopied the lanceolate complex deficits observed in Ntng1 mutants. Moreover, NGL-1-Netrin-G1 signaling is a general mediator of LTMR end organ formation across diverse tissue types demonstrated by the fact that Aß RA-LTMR endings associated with Meissner corpuscles and Pacinian corpuscles are also compromised in the Ntng1 and Lrrc4c mutant mice. Thus, axon-glia interactions, mediated in part by NGL-1-Netrin-G1 signaling, promote LTMR end organ formation.


Assuntos
Axônios , Mecanorreceptores , Animais , Axônios/metabolismo , Carotenoides , Ligantes , Mecanorreceptores/fisiologia , Camundongos , Netrinas/genética , Netrinas/metabolismo , Células de Schwann , Pele , Vitamina A/análogos & derivados
14.
J Neurosci Methods ; 382: 109724, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36207004

RESUMO

BACKGROUND: The analysis of ligamentous mechanoreceptors is difficult due to a high amount of unclassifiable mechanoreceptors, which result from incomplete visualization through limited microscopic techniques. NEW METHOD: The method was developed using dorsal intercarpal ligaments and dorsal regions of the scapholunate interosseous ligament from human cadaver wrists. Consecutive 70 µm thick cryosections were stained with immunofluorescence markers for protein S100B, neurotrophin receptor p75 (p75), protein gene product 9.5 (PGP 9.5) and 4',6-diamidino-2-phenylindole (DAPI). 3D images of sensory nerve endings were obtained using a confocal laser scanning microscope. Experimental point spread functions (PSF) were used to deconvolve images. Sensory nerve endings were localised in each section plane and classified according to Freeman and Wyke. Finally, confocal data was visualized as 3D-images. RESULTS: The method produced excellent image quality, revealing detailed three-dimensional structures. The created 3D-model of sensory nerve endings could be analyzed in all three dimensions, augmenting visualization of the form and immunoreactive pattern of sensory nerve endings. Deconvolution with experimentally measured PSFs aided in enhancing image quality. COMPARISON WITH EXISTING METHODS: Using a triple immunofluorescent staining method allows to visualize the structure of sensory nerve endings more precisely than techniques with serial analysis of different monostaining of neural markers. Imaging in three dimensions enhances morphologic details, which are limited in 2D-microscopy. CONCLUSION: 3D-triple immunofluorescence produces high quality visualization of mechanoreceptors, thereby improving their analysis. As an elaborate technique, it is ideal for defined research questions concerning the microstructure of sensory nerve endings.


Assuntos
Mecanorreceptores , Células Receptoras Sensoriais , Humanos , Imunofluorescência , Mecanorreceptores/fisiologia , Ligamentos Articulares/inervação , Ligamentos Articulares/metabolismo , Coloração e Rotulagem
15.
Rev. bras. ortop ; 57(5): 863-867, Sept.-Oct. 2022. graf
Artigo em Inglês | LILACS | ID: biblio-1407705

RESUMO

Abstract Objectives The capsuloligamentous structures of the shoulder work as static stabilizers, together with the biceps and rotator cuff muscles, increasing the contact surface of the glenoid cavity. Free nerve endings and mechanoreceptors have been identified in the shoulder; however, there are a few studies that describe the presence of these nerves in the biceps' insertion. The present study aimed to describe the morphology and distribution of nerve endings using immunofluorescence with protein gene product 9.5 (PGP 9.5) and confocal microscopy. Methods Six labrum-biceps complexes from six fresh-frozen cadavers were studied. The specimens were coronally cut and prepared using the immunofluorescence technique. In both hematoxylin and eosin (H&E) and immunofluorescence, the organization of the connective tissue with parallel collagen fibers was described. Results In the H&E study, vascular structures and some nerve structures were visualized, which were identified by the elongated presence of the nerve cell. All specimens analyzed with immunofluorescence and confocal microscopy demonstrated poor occurrence of morphotypes of sensory corpuscles and free nerve endings. We identified free nerve endings located in the labrum and in the bicipital insertion, and sparse nerve endings along the tendon. Corpuscular endings with fusiform, cuneiform, and oval aspect were identified in the tendon. Conclusion These findings support the hypothesis that the generation of pain in the superior labral tear from Anterior to posterior (SLAP) lesions derives from the more proximal part of the long biceps cord and even more from the upper labrum. Future quantitative studies with a larger number of specimens may provide more information on these sensory systems.


Resumo Objetivos As estruturas capsulo-ligamentares do ombro funcionam como estabilizadores estáticos, juntamente com os músculos do bíceps e do manguito rotador, aumentando a superfície de contato da cavidade glenoide. Terminações nervosas livres e mecanorreceptores foram identificados no ombro; no entanto, existem alguns estudos que descrevem a presença desses nervos na inserção do bíceps. Este estudo teve como objetivo descrever a morfologia e distribuição de terminações nervosas utilizando imunofluorescência com protein gene product 9.5 (PGP 9.5) e microscopia confocal. Métodos Foram estudados seis complexos labrum-bíceps de seis cadáveres congelados frescos. Os espécimes foram cortados coronalmente e preparados pelo método de imunofluorescência. Tanto em hematoxilina e eosina (H&E) quanto em imunofluorescência, foi descrita a organização do tecido conjuntivo com fibras paralelas de colágeno. Resultados No estudo de H&E, foram visualizadas estruturas vasculares e algumas estruturas nervosas, que foram identificadas pela presença alongada da célula nervosa. Todas as amostras analisadas com imunofluorescência e microscopia confocal demonstraram baixa ocorrência de morfotipos de corpúsculos sensoriais e terminações nervosas livres. Identificamos terminações nervosas livres localizadas no labrum, inserção bicipital e terminações nervosas esparsas ao longo do tendão. Terminais corpusculares com aspecto fusiforme, cuneiforme e oval foram identificados no tendão. Conclusão Esses achados corroboram a hipótese de que a geração de dor nas lesões labrais superiores de anterior a posterior (SLAP, na sigla em inglês) deriva da parte mais proximal do cabo longo do bíceps e ainda mais do labrum superior. Estudos quantitativos futuros com um número maior de espécimes podem fornecer mais informações sobre esses sistemas sensoriais.


Assuntos
Humanos , Articulação do Ombro , Cadáver , Imunofluorescência , Músculos Isquiossurais , Mecanorreceptores , Terminações Nervosas
16.
Front Endocrinol (Lausanne) ; 13: 995499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120469

RESUMO

During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT's anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [siPiezo1; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in siPiezo1 cells but not in NC; in contrast, siPiezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.


Assuntos
Adipogenia , Hipertensão , Tecido Adiposo/metabolismo , Animais , Cálcio/metabolismo , Masculino , Mecanorreceptores/metabolismo , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley
17.
Neuroreport ; 33(14): 617-622, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062515

RESUMO

Somatosensory information is signaled by primary sensory neurons located in dorsal root ganglia (DRG) or trigeminal ganglia. Type C-low threshold mechanoreceptors (C-LTMRs) are proposed to sense light touch. The differentiation and maturation of C-LTMRs are regulated by multiple transcript factors, including Zfp521 and Runx1. However, the molecular mechanism of C-LTMR development still remains largely unclear. RNA sequencing (RNA-seq) was performed to detect transcriptional changes in Tlx3cko DRGs compared to controls. In situ hybridization and RNAscope were used to verify RNA-seq data. RNA-seq identified 203 up- and 372 downregulated genes in DRG by loss of Tlx3 function. KEGG and Gene ontology analysis indicated that the biological properties and molecular functions were closely associated with neural signal processing and transmitting somatosensory information. In addition, the expression of marker genes of C-LTMRs was significantly decreased in Tlx3 mutants. However, Tlx3cko mice exhibited normal response to static and dynamic touch. Furthermore, Tlx3 was required to regulate the expression of Zfp521 and Runx1. Tlx3, Runx1 and Zfp521 may form a hierarchical regulation pathway to control C-LTMR development.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Proteínas de Homeodomínio/metabolismo , Mecanorreceptores , Animais , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Gânglios Espinais/metabolismo , Mecanorreceptores/metabolismo , Camundongos
18.
Sensors (Basel) ; 22(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36081155

RESUMO

Tactile sensing has attracted significant attention as a tactile quantitative evaluation method because the tactile sensation is an important factor while evaluating consumer products. Although the human tactile perception mechanism has nonlinearity, previous studies have often developed linear regression models. In contrast, this study proposes a nonlinear tactile estimation model that can estimate sensory evaluation scores from physical measurements. We extracted features from the vibration data obtained by a tactile sensor based on the perceptibility of mechanoreceptors. In parallel, a sensory evaluation test was conducted using 10 evaluation words. Then, the relationship between the extracted features and the tactile evaluation results was modeled using linear/nonlinear regressions. The best model was concluded by comparing the mean squared error between the model predictions and the actual values. The results imply that there are multiple evaluation words suitable for adopting nonlinear regression models, and the average error was 43.8% smaller than that of building only linear regression models.


Assuntos
Percepção do Tato , Tato , Humanos , Modelos Lineares , Mecanorreceptores , Vibração
19.
Am J Physiol Cell Physiol ; 323(4): C959-C973, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35968892

RESUMO

Mechanosensitive cation channels and Ca2+ influx through these channels play an important role in the regulation of endothelial cell functions. Transient receptor potential canonical channel 6 (TRPC6) is a diacylglycerol-sensitive nonselective cation channel that forms receptor-operated Ca2+ channels in a variety of cell types. Piezo1 is a mechanosensitive cation channel activated by membrane stretch and shear stress in lung endothelial cells. In this study, we report that TRPC6 and Piezo1 channels both contribute to membrane stretch-mediated cation currents and Ca2+ influx or increase in cytosolic-free Ca2+ concentration ([Ca2+]cyt) in human pulmonary arterial endothelial cells (PAECs). The membrane stretch-mediated cation currents and increase in [Ca2+]cyt in human PAECs were significantly decreased by GsMTX4, a blocker of Piezo1 channels, and by BI-749327, a selective blocker of TRPC6 channels. Extracellular application of 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane permeable analog of diacylglycerol, rapidly induced whole cell cation currents and increased [Ca2+]cyt in human PAECs and human embryonic kidney (HEK)-cells transiently transfected with the human TRPC6 gene. Furthermore, membrane stretch with hypo-osmotic or hypotonic solution enhances the cation currents in TRPC6-transfected HEK cells. In HEK cells transfected with the Piezo1 gene, however, OAG had little effect on the cation currents, but membrane stretch significantly enhanced the cation currents. These data indicate that, while both TRPC6 and Piezo1 are involved in generating mechanosensitive cation currents and increases in [Ca2+]cyt in human PAECs undergoing mechanical stimulation, only TRPC6 (but not Piezo1) is sensitive to the second messenger diacylglycerol. Selective blockers of these channels may help develop novel therapies for mechanotransduction-associated pulmonary vascular remodeling in patients with pulmonary arterial hypertension.


Assuntos
Células Endoteliais , Canais Iônicos , Mecanorreceptores , Canal de Cátion TRPC6 , Cálcio/metabolismo , Cátions/metabolismo , Diglicerídeos/metabolismo , Diglicerídeos/farmacologia , Células Endoteliais/metabolismo , Humanos , Soluções Hipotônicas/metabolismo , Soluções Hipotônicas/farmacologia , Canais Iônicos/genética , Canais Iônicos/metabolismo , Mecanorreceptores/metabolismo , Mecanotransdução Celular/genética , Mecanotransdução Celular/fisiologia , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo
20.
J Anat ; 241(4): 966-980, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35938671

RESUMO

Ibises (order: Pelecaniformes, family: Threskiornithidae) are probe-foraging birds that use 'remote-touch' to locate prey items hidden in opaque substrates. This sensory capability allows them to locate their prey using high-frequency vibrations in the substrate in the absence of other sensory cues. Remote-touch is facilitated by a specialised bill-tip organ, comprising high densities of mechanoreceptors (Herbst corpuscles) embedded in numerous foramina in the beak bones. Each foramen and its associated Herbst corpuscles make up a sensory unit, called a 'sensory pit'. These sensory pits are densely clustered in the distal portion of the beak. Previous research has indicated that interspecific differences in the extent of sensory pitting in the beak bones correlate with aquatic habitat use of ibises, and have been suggested to reflect different levels of remote-touch sensitivity. Our study investigates the interspecific differences in the bone and soft tissue histology of the bill-tip organs of three species of southern African ibises from different habitats (mainly terrestrial to mainly aquatic). We analysed the external pitting pattern on the bones, as well as internal structure of the beak using micro-CT scans and soft tissue histological sections of each species' bill-tip organs. The beaks of all three species contain remote-touch bill-tip organs and are described here in detail. Clear interspecific differences are evident between the species' bill-tip organs, both in terms of bone morphology and soft tissue histology. Glossy Ibises, which forage exclusively in wetter substrates, have a greater extent of pitting but lower numbers of Herbst corpuscles in each pit, while species foraging in drier substrates (Hadeda and Sacred Ibises) have more robust beaks, fewer pits and higher densities of Herbst corpuscles. Our data, together with previously published histological descriptions of the bill-tip organs of other remote-touch foraging bird species, indicate that species foraging in drier habitats have more sensitive bill-tip organs (based on their anatomy). The vibrations produced by prey (e.g., burrowing invertebrates) travel poorly in dry substrates compared with wetter ones (i.e., dry soil vs. mud or water), and thus we hypothesise that a more sensitive bill-tip organ may be required to successfully locate prey in dry substrates. Furthermore, our results indicate that the differences in bill-tip organ anatomy between the species reflect complex trade-offs between morphological constraints of beak shape and remote-touch sensitivity requirements, both of which are likely related to each species' foraging behaviour and substrate usage. Our study suggests that structures in the bone of the bill-tip organ could provide valuable osteological correlates for the associated soft tissues, and consequently may provide information on the sensory ecology and habitat usage of the birds in the absence of soft tissues.


Assuntos
Bico/anatomia & histologia , Aves/anatomia & histologia , Tato , África Austral , Animais , Bico/fisiologia , Aves/fisiologia , Mecanorreceptores/fisiologia , Solo , Tato/fisiologia , Vibração , Água
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