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1.
Geriatr Gerontol Int ; 24 Suppl 1: 320-326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38267253

RESUMO

AIM: To examine the actual conditions of older patients receiving home medical care after hospitalization over a period of 2 years in Japan. METHODS: The study population included 102 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan over a period of 2 years. We investigated the actual conditions for returning home after hospitalization. RESULTS: The median age of the 102 participants was 84 years, and 61 (59.8%) were women. In the group that returned home, 42 (55.3%) of the respondents desired to recuperate in a familiar place, as in advanced care planning (ACP). During the 2-year follow-up period, the group that did not return home had significantly more deaths. A multivariate analysis showed the association in the presence of ACP (odds ratio: 4.72, 95% confidence interval: 1.60-13.86) and cardiac disease (odds ratio: 0.25, 95% confidence interval: 0.08-0.76). The lack of ACP in the medical records when the patient was admitted to the hospital may have prevented the return home. CONCLUSION: In older patients who had difficulty returning home after hospitalization, the lack of ACP in home medical care may have been an influencing factor. ACP could help continue with home medical care. Geriatr Gerontol Int 2024; 24: 320-326.


Assuntos
Serviços de Assistência Domiciliar , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Japão , Hospitalização , Hospitais
2.
Proc Natl Acad Sci U S A ; 119(21): e2115821119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35580186

RESUMO

Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channel­mediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].


Assuntos
Canais Iônicos , Neurônios , Sistema Nervoso Periférico , Estimulação Elétrica Nervosa Transcutânea , Potenciais de Ação , Animais , Interneurônios , Mamíferos , Neurônios/fisiologia , Sistema Nervoso Periférico/fisiologia , Ultrassonografia/métodos
3.
Nihon Ronen Igakkai Zasshi ; 58(4): 602-609, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34880179

RESUMO

AIM: We investigated seasonal variations in blood pressure (BP) and factors related to these variations among older patients receiving home medical care. METHOD: A total 57 patients ≥ 65 years old receiving home medical care who participated in the Osaka Home Care REgistry study (OHCARE), a prospective cohort study, were included. We investigated the seasonal patient characteristics and variations in the BP. In addition, to determine the influence of seasonal variations in the systolic blood pressure (SBP) on the occurrence of clinical events (hospitalization, falls and death), we classified patients into larger- and smaller- change groups based on the median seasonal variations in SBP. RESULT: About 60% of subjects were very frail or bedridden. The mean BP was higher in winter than in summer (124.7±11/69.5±7 vs.120.5±12/66.9±8 mmHg) (P< 0.01). On comparing the characteristics of the two groups with larger and smaller changes in the SBP, the group with large BP changes had a significantly lower BP in summer than the group with small BP changes. In addition, the incidence of "hospitalization" was significantly higher in the group with large BP changes than in the group with small BP changes (P = 0.03). CONCLUSION: The present study revealed that there were seasonal changes in the BP in older patients receiving home medical care. It was also suggested that seasonal changes in the BP might be associated with the risk of hospitalization events. Given these BP variations, doctors and visiting nurses should be alert for systemic abnormalities, especially in frail patients receinving home medical care.


Assuntos
Serviços de Assistência Domiciliar , Hipertensão , Idoso , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Estudos Prospectivos , Estações do Ano
4.
Hypertens Res ; 44(2): 197-205, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32873899

RESUMO

Some studies reported that excessive blood pressure (BP) control was not appropriate for older people, especially from the viewpoint of quality of life and maintaining sufficient blood flow for tissue perfusion. However, the lower limit of the target BP is still unclear, and there has not yet been a sufficient consensus. Therefore, we investigated the associations of BP levels with clinical events in older patients ~85 years old receiving home medical care. A total of 144 patients were included, who were followed for longer than 3 months in the Osaka Home Care Registry study, a prospective cohort study targeting older patients receiving home medical care in Japan. BP levels were divided into lower and higher groups based on the average systolic blood pressure (SBP). The main outcomes were clinical events, including hospitalizations, falls, and deaths during follow-up. As a result, the hospitalization rate in the SBP below 124 mmHg group was significantly higher than that in the SBP over 124 mmHg group. When comparing the clinical events between the two groups only in participants with hypertension, the same results were obtained. Furthermore, in Cox proportional hazards regression models adjusted by age, sex, and current diseases, the SBP below 124 mmHg group showed a significantly higher rate of required hospitalization (hazard ratio: 7.25, 95% confidence interval: 1.79-29.45). Thus, in older and very frail patients requiring home medical care, an SBP level below 124 mmHg could be a predictive marker of clinical events leading to hospitalization.


Assuntos
Serviços de Assistência Domiciliar , Hipertensão , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Humanos , Hipertensão/epidemiologia , Estudos Prospectivos , Qualidade de Vida
5.
Geriatr Gerontol Int ; 19(12): 1198-1205, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31674723

RESUMO

AIM: To clarify factors associated with changes in care needs level and mortality among disabled older people receiving home medical care over a period of 2.5 years. METHODS: The study included 179 participants, aged ≥65 years, receiving home medical care, who consented to join the Osaka Home Care Registry study. The main outcome was changes in the care needs level of participants eligible for the long-term care insurance system. We investigated the association of changes in care needs level with basic characteristics and care-receiving status. RESULTS: At the 2.5-year follow up, 20.0% of participants showed deteriorated levels, and 41.8% of participants died. In multiple logistic regression, age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.00-1.21; P = 0.051) and bone joint diseases (OR 0.34, CI 0.09-1.22; P = 0.098) were possible risks associated with deterioration of the care needs level. Male sex (OR 3.28, CI 0.91-11.74; P = 0.068) was a possible risk factor for mortality, and lower serum albumin (OR 0.22, CI 0.07-0.73) was a significant risk factor for mortality. CONCLUSIONS: We clarified the different factors associated with deterioration of the care needs level and mortality among disabled older people. Old age and bone joint diseases might be predictive factors for the further deterioration of independence of physical activity, and a low serum albumin level is considered to be strongly associated with increased mortality. Geriatr Gerontol Int 2019; 19: 1198-1205.


Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Avaliação das Necessidades , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Seguro de Assistência de Longo Prazo/estatística & dados numéricos , Japão , Masculino , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo
6.
Nihon Ronen Igakkai Zasshi ; 56(4): 468-477, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31761853

RESUMO

AIM: The present study investigated the behavioral and psychological symptoms of dementia (BPSD) and pharmacological therapy among elderly people with dementia who received home medical treatment. METHODS: This study was part of the Osaka Home Care Registry study (OHCARE-study). Participants were >65 years old with dementia. Demographic and medical data, BPSD, and the LTCI [long-term care insurance] care-need level were collected. A multiple logistic regression analysis was performed in order to clarify the factors associated with BPSD. RESULTS: Among 110 subjects (82.0±11.3 years old), 64.6% had a diagnosis of dementia, most commonly Alzheimer's dementia. Aside from home medical treatment, 58.1% had a nurse visit, 48.1% received home care, and 40.0% used a day service. The prevalence of BPSD was 53.0%. Those with BPSD most frequently had an LTCI care-need level of 3, and the prevalence of BPSD declined as the level increased after 3. Psychotropic drugs were prescribed in 61.5% of those with BPSD. Antipsychotic drugs were used significantly more frequently in those with nursing care resistance, assault and delusions than in others (all, p <0.005). A multivariate analysis showed that the positive predictor of BPSD was antipsychotic drug use, while negative predictors were an LTCI care-need level and the use of visiting rehabilitation. CONCLUSION: The BPSD in elderly dementia patients receiving home medical treatment were clarified. The LTCI care-need level is an independent predictor of BPSD after adjusting for the activities of daily life. Further longitudinal investigations including the BPSD severity and frequency are needed.


Assuntos
Doença de Alzheimer , Demência , Serviços de Assistência Domiciliar , Seguro de Assistência de Longo Prazo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Estudos Transversais , Demência/psicologia , Demência/terapia , Humanos
7.
Neuron ; 100(6): 1401-1413.e6, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30415995

RESUMO

Epithelial-neuronal signaling is essential for sensory encoding in touch, itch, and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as a framework to test this hypothesis. RNA sequencing of adult mouse Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogs. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of ß2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch. VIDEO ABSTRACT.


Assuntos
Adrenérgicos/metabolismo , Vias Aferentes/fisiologia , Células de Merkel/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Animais , Cápsulas Bacterianas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Feminino , Gânglios Espinais/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores Adrenérgicos beta 2 , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores 5-HT3 de Serotonina/genética , Receptores 5-HT3 de Serotonina/metabolismo , Pele/citologia , Pele/inervação , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/genética , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Proteína Wnt1/genética , Proteína Wnt1/metabolismo
8.
Cell Rep ; 17(7): 1719-1727, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27829143

RESUMO

Sensory tissues exposed to the environment, such as skin, olfactory epithelia, and taste buds, continuously renew; therefore, peripheral neurons must have mechanisms to maintain appropriate innervation patterns. Although somatosensory neurons regenerate after injury, little is known about how these neurons cope with normal target organ changes. To elucidate neuronal plasticity in healthy skin, we analyzed the structure of Merkel-cell afferents, which are gentle touch receptors, during skin remodeling that accompanies mouse hair-follicle regeneration. The number of Merkel cells is reduced by 90% and axonal arbors are simplified during active hair growth. These structures rebound within just days. Computational modeling predicts that Merkel-cell changes are probabilistic, but myelinated branch stability depends on Merkel-cell inputs. Electrophysiology and behavior demonstrate that tactile responsiveness is less reliable during active growth than in resting skin. These results reveal that somatosensory neurons display structural plasticity at the cost of impairment in the reliability of encoding gentle touch.


Assuntos
Receptores de Superfície Celular/metabolismo , Pele/metabolismo , Tato/fisiologia , Animais , Comportamento Animal , Simulação por Computador , Cabelo/crescimento & desenvolvimento , Células de Merkel/metabolismo , Camundongos Endogâmicos C57BL
9.
J Neurophysiol ; 116(1): 218-28, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27098029

RESUMO

Distinct patterns in neuronal firing are observed between classes of cutaneous afferents. Such differences may be attributed to end-organ morphology, distinct ion-channel complements, and skin microstructure, among other factors. Even for just the slowly adapting type I afferent, the skin's mechanics for a particular specimen might impact the afferent's firing properties, especially given the thickness and elasticity of skin can change dramatically over just days. Here, we show computationally that the skin can reliably convey indentation magnitude, rate, and spatial geometry to the locations of tactile receptors even amid changes in skin's structure. Using finite element analysis and neural dynamics models, we considered the skin properties of six mice that span a representative cohort. Modeling the propagation of the surface stimulus to the interior of the skin demonstrated that there can be large variance in stresses and strains near the locations of tactile receptors, which can lead to large variance in static firing rate. However, variance is significantly reduced when the stimulus tip is controlled by surface pressure and compressive stress is measured near the end organs. This particular transformation affords the least variability in predicted firing rates compared with others derived from displacement, force, strain energy density, or compressive strain. Amid changing skin mechanics, stimulus control by surface pressure may be more naturalistic and optimal and underlie how animals actively explore the tactile environment.


Assuntos
Simulação por Computador , Mecanorreceptores/fisiologia , Modelos Biológicos , Pressão , Fenômenos Fisiológicos da Pele , Pele/inervação , Potenciais de Ação , Animais , Fenômenos Biomecânicos , Feminino , Análise de Elementos Finitos , Camundongos Transgênicos , Técnicas de Cultura de Tecidos
10.
PLoS One ; 10(3): e0120897, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25803703

RESUMO

Although the skin's mechanical properties are well characterized in tension, little work has been done in compression. Here, the viscoelastic properties of a population of mouse skin specimens (139 samples from 36 mice, aged 5 to 34 weeks) were characterized upon varying specimen thickness, as well as strain level and rate. Over the population, we observed the skin's viscoelasticity to be quite variable, yet found systematic correlation of residual stress ratio with skin thickness and strain, and of relaxation time constants with strain rates. In particular, as specimen thickness ranged from 211 to 671 µm, we observed significant variation in both quasi-linear viscoelasticity (QLV) parameters, the relaxation time constant (τ1 = 0.19 ± 0.10 s) and steady-state residual stress ratio (G∞ = 0.28 ± 0.13). Moreover, when τ1 was decoupled and fixed, we observed that G∞ positively correlated with skin thickness. Second, as steady-state stretch was increased (λ∞ from 0.22 to 0.81), we observed significant variation in both QLV parameters (τ1 = 0.26 ± 0.14 s, G∞ = 0.47 ± 0.17), and when τ1 was fixed, G∞ positively correlated with stretch level. Third, as strain rate was increased from 0.06 to 22.88 s-1, the median time constant τ1 varied from 1.90 to 0.31 s, and thereby negatively correlated with strain rate. These findings indicate that the natural range of specimen thickness, as well as experimental controls of compression level and rate, significantly influence measurements of skin viscoelasticity.


Assuntos
Pele/química , Animais , Força Compressiva , Simulação por Computador , Elasticidade , Camundongos , Modelos Biológicos , Estresse Mecânico , Viscosidade
11.
Pflugers Arch ; 467(1): 101-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25053537

RESUMO

The cellular and molecular basis of vertebrate touch reception remains least understood among the traditional five senses. Somatosensory afferents that innervate the skin encode distinct tactile qualities, such as flutter, slip, and pressure. Gentle touch is thought to be transduced by somatosensory afferents whose tactile end organs selectively filter mechanical stimuli. These tactile end organs comprise afferent terminals in association with non-neuronal cell types such as Merkel cells, keratinocytes, and Schwann cells. An open question is whether these non-neuronal cells serve primarily as passive mechanical filters or whether they actively participate in mechanosensory transduction. This question has been most extensively studied in Merkel cells, which are epidermal cells that complex with sensory afferents in regions of high tactile acuity such as fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes mediate slowly adapting type I (SAI) responses, which encode sustained pressure and represent object features with high fidelity. How Merkel cells contribute to unique SAI firing patterns has been debated for decades; however, three recent studies in rodent models provide some direct answers. First, whole-cell recordings demonstrate that Merkel cells are touch-sensitive cells with fast, mechanically activated currents that require Piezo2. Second, optogenetics and intact recordings show that Merkel cells mediate sustained SAI firing. Finally, loss-of-function studies in transgenic mouse models reveal that SAI afferents are also touch sensitive. Together, these studies identify molecular mechanisms of mechanotransduction in Merkel cells, reveal unexpected functions for these cells in touch, and support a revised, two-receptor site model of mechanosensory transduction.


Assuntos
Epiderme/fisiologia , Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Células de Merkel/fisiologia , Tato/fisiologia , Animais , Comunicação Celular/fisiologia , Células Epidérmicas , Humanos , Modelos Biológicos
12.
Nature ; 509(7502): 622-6, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24717433

RESUMO

How we sense touch remains fundamentally unknown. The Merkel cell-neurite complex is a gentle touch receptor in the skin that mediates slowly adapting responses of Aß sensory fibres to encode fine details of objects. This mechanoreceptor complex was recognized to have an essential role in sensing gentle touch nearly 50 years ago. However, whether Merkel cells or afferent fibres themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown. Synapse-like junctions are observed between Merkel cells and associated afferents, and yet it is unclear whether Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighbouring nerve. Here we show that Merkel cells produce touch-sensitive currents in vitro. Piezo2, a mechanically activated cation channel, is expressed in Merkel cells. We engineered mice deficient in Piezo2 in the skin, but not in sensory neurons, and show that Merkel-cell mechanosensitivity completely depends on Piezo2. In these mice, slowly adapting responses in vivo mediated by the Merkel cell-neurite complex show reduced static firing rates, and moreover, the mice display moderately decreased behavioural responses to gentle touch. Our results indicate that Piezo2 is the Merkel-cell mechanotransduction channel and provide the first line of evidence that Piezo channels have a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor-site model, in which both Merkel cells and innervating afferents act together as mechanosensors. The two-receptor system could provide this mechanoreceptor complex with a tuning mechanism to achieve highly sophisticated responses to a given mechanical stimulus.


Assuntos
Canais Iônicos/metabolismo , Mecanotransdução Celular , Células de Merkel/metabolismo , Tato/fisiologia , Potenciais de Ação , Animais , Condutividade Elétrica , Feminino , Técnicas In Vitro , Canais Iônicos/deficiência , Canais Iônicos/genética , Masculino , Mecanotransdução Celular/genética , Camundongos , Camundongos Knockout , Neuritos/metabolismo , Neurônios Aferentes/metabolismo , Pele/citologia , Pele/inervação , Tato/genética
13.
Nature ; 509(7502): 617-21, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24717432

RESUMO

Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.


Assuntos
Vias Aferentes , Células Epidérmicas , Epiderme/inervação , Mecanotransdução Celular , Células de Merkel/metabolismo , Tato/fisiologia , Potenciais de Ação , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Condutividade Elétrica , Feminino , Canais Iônicos/metabolismo , Masculino , Camundongos , Modelos Biológicos , Neuritos/metabolismo , Neurônios Aferentes/metabolismo , Optogenética , Pressão
14.
Elife ; 3: e01488, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24448409

RESUMO

Touch is encoded by cutaneous sensory neurons with diverse morphologies and physiological outputs. How neuronal architecture influences response properties is unknown. To elucidate the origin of firing patterns in branched mechanoreceptors, we combined neuroanatomy, electrophysiology and computation to analyze mouse slowly adapting type I (SAI) afferents. These vertebrate touch receptors, which innervate Merkel cells, encode shape and texture. SAI afferents displayed a high degree of variability in touch-evoked firing and peripheral anatomy. The functional consequence of differences in anatomical architecture was tested by constructing network models representing sequential steps of mechanosensory encoding: skin displacement at touch receptors, mechanotransduction and action-potential initiation. A systematic survey of arbor configurations predicted that the arrangement of mechanotransduction sites at heminodes is a key structural feature that accounts in part for an afferent's firing properties. These findings identify an anatomical correlate and plausible mechanism to explain the driver effect first described by Adrian and Zotterman. DOI: http://dx.doi.org/10.7554/eLife.01488.001.


Assuntos
Simulação por Computador , Mecanorreceptores/ultraestrutura , Mecanotransdução Celular , Modelos Neurológicos , Rede Nervosa/ultraestrutura , Pele/inervação , Tato , Potenciais de Ação , Adaptação Fisiológica , Animais , Potenciais Evocados , Feminino , Mecanorreceptores/fisiologia , Células de Merkel/fisiologia , Células de Merkel/ultraestrutura , Camundongos Transgênicos , Microscopia Confocal , Rede Nervosa/fisiologia , Técnicas de Rastreamento Neuroanatômico , Fatores de Tempo
15.
PLoS One ; 8(6): e67439, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23825661

RESUMO

The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus). These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6-10 weeks) and intermediate (13-19 weeks) adult ages but by body weight in mature mice (26-34 weeks). Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given location maintains a constant elastic modulus to compression throughout normal physiological stages.


Assuntos
Elasticidade , Fenômenos Fisiológicos da Pele , Animais , Camundongos
16.
Ann N Y Acad Sci ; 1279: 13-21, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23530998

RESUMO

Merkel cells are an enigmatic group of rare cells found in the skin of vertebrates. Most make contacts with somatosensory afferents to form Merkel cell-neurite complexes, which are gentle-touch receptors that initiate slowly adapting type I responses. The function of Merkel cells within the complex remains debated despite decades of research. Numerous anatomical studies demonstrate that Merkel cells form synaptic-like contacts with sensory afferent terminals. Moreover, recent molecular analysis reveals that Merkel cells express dozens of presynaptic molecules that are essential for synaptic vesicle release in neurons. Merkel cells also produce a host of neuroactive substances that can act as fast excitatory neurotransmitters or neuromodulators. Here, we review the major neurotransmitters found in Merkel cells and discuss these findings in relation to the potential function of Merkel cells in touch reception.


Assuntos
Células de Merkel/fisiologia , Neuritos/fisiologia , Neurotransmissores/fisiologia , Células Receptoras Sensoriais/fisiologia , Sinapses/fisiologia , Animais , Comunicação Celular/fisiologia , Humanos , Células de Merkel/metabolismo , Modelos Biológicos , Neuritos/metabolismo , Neurotransmissores/metabolismo , Células Receptoras Sensoriais/metabolismo , Sinapses/metabolismo , Tato/fisiologia
17.
World Haptics Conf ; 2013: 645-650, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24500653

RESUMO

The neural response to touch stimuli is influenced by skin properties as well as the delivery of stimuli. Here, we compare stimuli controlled by displacement and force, and analyze the impact on firing rates of slowly adapting type I afferents as skin thickness and elasticity change. Uniaxial compression tests were used to measure the mechanical properties of mouse hind limb skin (n=5), resulting in a range of skin thickness measurements (211.6-530.6 µm) and hyper- and visco-elastic properties (average coefficient of variation=0.27).Values were integrated to an axisymmetric finite element model using an Ogden strain energy function. This calculated the propagation of surface loads to tactile end-organ locations, where maximum compressive stress and its rate were sampled and linearly regressed to firing rate. For the observed range of skin thickness, firing response was predicted under both force and displacement control of a ramp-and-hold stimulus. Over the ramp phase of stimulation, the variance in predicted firing rate was higher under displacement than under force control (22.2versus 4.9 Hz) with a similar trend in the sustained phase of stimulation (4.6versus1.3Hz). Given that skin thickness varies significantly between specimens, for human skin perhaps seven more so than for mice, the use of force control is predicted to decrease experimental variance in neurophysiological and psychophysical responses.

18.
Development ; 139(4): 740-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22241839

RESUMO

The piloneural collar in mammalian hairy skin comprises an intricate pattern of circumferential and longitudinal sensory afferents that innervate primary and secondary pelage hairs. The longitudinal afferents tightly associate with terminal Schwann cell processes to form encapsulated lanceolate nerve endings of rapidly adapting mechanoreceptors. The molecular basis for piloneural development, maintenance and function is poorly understood. Here, we show that Nefh-expressing glutamatergic neurons represent a major population of longitudinal and circumferential sensory afferents innervating the piloneural collar. Our findings using a VGLUT2 conditional-null mouse model indicate that glutamate is essential for innervation, patterning and differentiation of NMDAR(+) terminal Schwann cells during piloneural collar development. Similarly, treatment of adult mice with a selective NMDAR antagonist severely perturbed piloneural collar structure and reduced excitability of these mechanosensory neurons. Collectively, these results show that DRG-derived glutamate is essential for the proper development, maintenance and sensory function of the piloneural mechanoreceptor.


Assuntos
Ácido Glutâmico/metabolismo , Folículo Piloso/inervação , Mecanorreceptores/fisiologia , Pele/citologia , Pele/inervação , Animais , Feminino , Folículo Piloso/citologia , Folículo Piloso/embriologia , Folículo Piloso/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Pele/embriologia , Pele/crescimento & desenvolvimento , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
19.
Philos Trans R Soc Lond B Biol Sci ; 366(1581): 3006-15, 2011 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-21969682

RESUMO

Orthopteroid insects (cockroaches, crickets, locusts and related species) allow examination of active sensory processing in a comparative framework. Some orthopteroids possess long, mobile antennae endowed with many chemo- and mechanoreceptors. When the antennae are touched, an animal's response depends upon the identity of the stimulus. For example, contact with a predator may lead to escape, but contact with a conspecific may usually not. Active touch of an approaching object influences the likelihood that a discrimination of identity will be made. Using cockroaches, we have identified specific descending mechanosensory interneurons that trigger antennal-mediated escape. Crucial sensory input to these cells comes from chordotonal organs within the antennal base. However, information from other receptors on the base or the long antennal flagellum allows active touch to modulate escape probability based on stimulus identity. This is conveyed, at least to some extent, by textural information. Guidance of the antennae in active exploration depends on visual information. Some of the visual interneurons and the motor neurons necessary for visuomotor control have been identified. Comparisons across Orthoptera suggest an evolutionary model where subtle changes in the architecture of interneurons, and of sensorimotor control loops, may explain differing levels of vision-touch interaction in the active guidance of behaviour.


Assuntos
Antenas de Artrópodes/fisiologia , Comportamento Animal/fisiologia , Baratas/fisiologia , Mecanorreceptores/fisiologia , Tato/fisiologia , Animais , Evolução Biológica , Reação de Fuga/fisiologia
20.
Nephrol Dial Transplant ; 26(10): 3256-62, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21372256

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is caused by various risk factors of cardiovascular disease (CVD). The estimated glomerular filtration rate (eGFR) is commonly used for the evaluation of the renal function in patients with CKD; however, it is difficult to assess the pathogenesis of CKD and predict the renal prognosis accurately using only eGFR. The resistive index (RI) in renal Doppler ultrasonography (RDU) is thought to be a good indicator of renal vascular resistance caused by atherosclerosis. In the present study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage and predict the renal prognosis and investigated the correlation between RI and blood pressure (BP) fluctuations in patients with or without hypertension. METHODS: The total study population included 194 patients (mean age: 66.2 years), who underwent RDU in our hospital ward between February 2009 and July 2010. We investigated the correlation between RI and multiple clinical parameters, including ambulatory blood pressure monitoring (ABPM). RESULTS: RI significantly correlated with age, eGFR, diastolic BP, pulse pressure and level of albuminuria. Patients with diabetes mellitus (DM) showed a significantly higher RI than patients without DM, although their eGFR was similar; thus, DM might accelerate renal vascular damage and RI could detect earlier changes of vascular damage proceeding the time eGFR is reduced. Regarding ABPM, patients with a larger morning surge [systolic blood pressure (SBP) in the early morning--lowest SBP during sleep] showed a significantly higher RI. CONCLUSIONS: The present study indicated that RI might be very useful for the evaluation of very early renal damage more effectively than eGFR and that diurnal BP change might be partly due to the progression of atherosclerotic change in the kidney evaluated by RI.


Assuntos
Aterosclerose/complicações , Rim/diagnóstico por imagem , Rim/fisiopatologia , Insuficiência Renal/diagnóstico , Ultrassonografia Doppler/estatística & dados numéricos , Resistência Vascular , Idoso , Aterosclerose/diagnóstico por imagem , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/fisiopatologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/metabolismo , Humanos , Rim/irrigação sanguínea , Testes de Função Renal , Masculino , Prognóstico , Insuficiência Renal/etiologia , Fatores de Risco
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