RESUMO
A crucial role of cortical networks is the conversion of sensory inputs into perception. In the cortical somatosensory network, neurons of the primary somatosensory cortex (S1) show invariant sensory responses, while frontal lobe neuronal activity correlates with the animal's perceptual behavior. Here, we report that in the secondary somatosensory cortex (S2), neurons with invariant sensory responses coexist with neurons whose responses correlate with perceptual behavior. Importantly, the vast majority of the neurons fall along a continuum of combined sensory and categorical dynamics. Furthermore, during a non-demanding control task, the sensory responses remain unaltered while the sensory information exhibits an increase. However, perceptual responses and the associated categorical information decrease, implicating a task context-dependent processing mechanism. Conclusively, S2 neurons exhibit intriguing dynamics that are intermediate between those of S1 and frontal lobe. Our results contribute relevant evidence about the role that S2 plays in the conversion of touch into perception.
Assuntos
Macaca mulatta/fisiologia , Neurônios/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/fisiologia , Percepção do Tato/fisiologia , Algoritmos , Animais , Lobo Frontal/citologia , Lobo Frontal/fisiologia , Modelos Neurológicos , Estimulação Física/métodos , Córtex Somatossensorial/citologiaRESUMO
AIMS: The present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties. MAIN METHODS: Male mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 × 106), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively. KEY FINDINGS: OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1ß and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-ß, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment. SIGNIFICANCE: MSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord.
Assuntos
Transplante de Células-Tronco Mesenquimais , Oxaliplatina/toxicidade , Oxirredução , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Células Receptoras Sensoriais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Interleucina-1beta/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Nociceptividade , Oxirredução/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/terapia , Reação em Cadeia da Polimerase em Tempo Real , Teste de Desempenho do Rota-Rod , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Peripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration. Nevertheless, the molecular alterations at the transcriptomic level associated with these compensatory growth mechanisms remain to be fully elucidated. We generated a surgical model of partial sciatic nerve injury in mice to mechanistically study degeneration-induced collateral sprouting from spared fibers in the peripheral nervous system. Using next-generation sequencing and Ingenuity Pathway Analysis, we described the sprouting-associated transcriptome of uninjured sensory neurons and compare it with the activated by regenerating neurons. In vitro approaches were used to functionally assess sprouting gene candidates in the mechanisms of axonal growth. Using a novel animal model, we provide the first description of the sprouting transcriptome observed in uninjured sensory neurons after nerve injury. This collateral sprouting-associated transcriptome differs from that seen in regenerating neurons, suggesting a molecular program distinct from axonal growth. We further demonstrate that genetic upregulation of novel sprouting-associated genes activates a specific growth program in vitro, leading to increased neuronal branching. These results contribute to our understanding of the molecular mechanisms associated with collateral sprouting in vivo. The data provided here will therefore be instrumental in developing therapeutic strategies aimed at promoting functional recovery after injury to the nervous system.
Assuntos
Perfilação da Expressão Gênica , Neurogênese/genética , Nervos Periféricos/fisiologia , Células Receptoras Sensoriais/fisiologia , Transcriptoma/genética , Animais , Proliferação de Células , Feminino , Gânglios Espinais/patologia , Regulação da Expressão Gênica , Vértebras Lombares/patologia , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Nervos Periféricos/ultraestrutura , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Células Receptoras Sensoriais/ultraestrutura , Degeneração Walleriana/genética , Degeneração Walleriana/patologiaRESUMO
Neuropathic and inflammatory pain results from cellular and molecular changes in dorsal root ganglion (DRG) neurons. The type-2 receptor for Angiotensin-II (AT2R) has been involved in this type of pain. However, the underlying mechanisms are poorly understood, including the role of the type-1 receptor for Angiotensin-II (AT1R). Here, we used a combination of immunohistochemistry and immunocytochemistry, RT-PCR and in vitro and in vivo pharmacological manipulation to examine how cutaneous inflammation affected the expression of AT1R and AT2R in subpopulations of rat DRG neurons and studied their impact on inflammation-induced neuritogenesis. We demonstrated that AT2R-neurons express C- or A-neuron markers, primarily IB4, trkA, and substance-P. AT1R expression was highest in small neurons and co-localized significantly with AT2R. In vitro, an inflammatory soup caused significant elevation of AT2R mRNA, whereas AT1R mRNA levels remained unchanged. In vivo, we found a unique pattern of change in the expression of AT1R and AT2R after cutaneous inflammation. AT2R increased in small neurons at 1 day and in medium size neurons at 4 days. Interestingly, cutaneous inflammation increased AT1R levels only in large neurons at 4 days. We found that in vitro and in vivo AT1R and AT2R acted co-operatively to regulate DRG neurite outgrowth. In vivo, AT2R inhibition impacted more on non-peptidergic C-neurons neuritogenesis, whereas AT1R blockade affected primarily peptidergic nerve terminals. Thus, cutaneous-induced inflammation regulated AT1R and AT2R expression and function in different DRG neuronal subpopulations at different times. These findings must be considered when targeting AT1R and AT2R to treat chronic inflammatory pain. Cover Image for this issue: doi: 10.1111/jnc.14737.
Assuntos
Dermatite/fisiopatologia , Receptor Tipo 1 de Angiotensina/fisiologia , Receptor Tipo 2 de Angiotensina/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Células Cultivadas , Dermatite/etiologia , Feminino , Adjuvante de Freund/administração & dosagem , Gânglios Espinais/citologia , Neuritos/fisiologia , Dor/fisiopatologia , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 2 de Angiotensina/análise , Células Receptoras Sensoriais/química , Pele/inervaçãoRESUMO
The cornea is extensively innervated by trigeminal ganglion cold thermoreceptor neurons expressing TRPM8 (transient receptor potential cation channel subfamily M member 8). These neurons respond to cooling, hyperosmolarity and wetness of the corneal surface. Surgical injury of corneal nerve fibers alters tear production and often causes dry eye sensation. The contribution of TRPM8-expressing corneal cold-sensitive neurons (CCSNs) to these symptoms is unclear. Using extracellular recording of CCSNs nerve terminals combined with in vivo confocal tracking of reinnervation, Ca2+ imaging and patch-clamp recordings of fluorescent retrogradely labeled corneal neurons in culture, we analyzed the functional modifications of CCSNs induced by peripheral axonal damage in male mice. After injury, the percentage of CCSNs, the cold- and menthol-evoked intracellular [Ca2+] rises and the TRPM8 current density in CCSNs were larger than in sham animals, with no differences in the brake K+ current IKD Active and passive membrane properties of CCSNs from both groups were alike and corresponded mainly to those of canonical low- and high-threshold cold thermoreceptor neurons. Ongoing firing activity and menthol sensitivity were higher in CCSN terminals of injured mice, an observation accounted for by mathematical modeling. These functional changes developed in parallel with a partial reinnervation of the cornea by TRPM8(+) fibers and with an increase in basal tearing in injured animals compared with sham mice. Our results unveil key TRPM8-dependent functional changes in CCSNs in response to injury, suggesting that increased tearing rate and ocular dryness sensation derived from deep surgical ablation of corneal nerves are due to enhanced functional expression of TRPM8 channels in these injured trigeminal primary sensory neurons.SIGNIFICANCE STATEMENT We unveil a key role of TRPM8 channels in the sensory and autonomic disturbances associated with surgical damage of eye surface nerves. We studied the damage-induced functional alterations of corneal cold-sensitive neurons using confocal tracking of reinnervation, extracellular corneal nerve terminal recordings, tearing measurements in vivo, Ca2+ imaging and patch-clamp recordings of cultured corneal neurons, and mathematical modeling. Corneal nerve ablation upregulates TRPM8 mainly in canonical cold thermoreceptors, enhancing their cold and menthol sensitivity, inducing a rise in the ongoing firing activity of TRPM8(+) nerve endings and an increase in basal tearing. Our results suggest that unpleasant dryness sensations, together with augmented tearing rate after corneal nerve injury, are largely due to upregulation of TRPM8 in cold thermoreceptor neurons.
Assuntos
Axônios/fisiologia , Temperatura Baixa , Córnea/inervação , Córnea/fisiologia , Células Receptoras Sensoriais/fisiologia , Canais de Cátion TRPM/fisiologia , Sensação Térmica/fisiologia , Animais , Lesões da Córnea/fisiopatologia , Fenômenos Eletrofisiológicos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Neurológicos , Modelos Teóricos , Fibras Nervosas , Técnicas de Patch-Clamp , Lágrimas , Termorreceptores/fisiologiaRESUMO
Sensory processes represent an information gathering interface between animals and their surrounding world. Therefore, they serve to scan the environment for resources and threats. The behavior of kissing bugs has been studied to aid their control because they transmit Chagas disease to humans. Besides, a few triatomines represent important insect models since Wigglesworth times. These hematophagous insects rely on different sensory systems to scan their environment for blood-sources, mating partners, and hiding places. The study of the molecular bases of sensory processes has undergone a dramatic progress due the advent of new technologies allowing mass-sequencing of genes. Here, we focus on reviewing the fundamental knowledge gathered to date about the molecular bases of kissing bug sensory processes.
Assuntos
Insetos Vetores/fisiologia , Rhodnius/fisiologia , Sensação , Células Receptoras Sensoriais/fisiologia , AnimaisRESUMO
The most broadly expressed and studied aspect of sensory transduction is receptor tuning to the power spectral density of the incoming signals. Temporal cues expressed in the phase spectrum are relevant in African and American pulse-emitting electric fish showing electroreceptors sensing the signals carried by the self- and conspecific-generated electric organ discharges. This article concerns the role of electroreceptor phase sensitivity in American pulse Gymnotiformes. These fish show electroreceptors sharply tuned to narrow frequency bands. This led to the common thought that most electrosensory information is contained in the amplitude spectra of the signals. However, behavioral and modeling studies suggest that in their pulses, Gymnotiformes electroreceptors also encode cues embodied in the phase spectrum of natural stimuli. Here, we show that the two main types of tuberous primary afferents of Gymnotus omarorum differentially respond to cues embodied in the amplitude and phase spectra of self-generated electrosensory signals. One afferent type, pulse markers, is mainly driven by the amplitude spectrum, while the other, burst coders, is predominantly sensitive to the phase spectrum. This dual encoding strategy allows the fish to create a sensory manifold where patterns of 'electric color' generated by object impedance and other potential sources of 'colored' images (such as large nearby objects and other electric fish) can be represented.
Assuntos
Órgão Elétrico/fisiologia , Gimnotiformes/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Impedância ElétricaRESUMO
Peripheral venous distension mechanically stimulates type III/IV sensory fibers in veins and evokes pressor and sympathoexcitatory reflex responses in humans. As young women have reduced venous compliance and impaired sympathetic transduction, we tested the hypothesis that pressor and sympathoexcitatory responses to venous distension may be attenuated in women compared with men. Mean arterial pressure (photoplethysmography), heart rate (HR), stroke volume (SV; Modelflow), cardiac output (CO = HR × SV), muscle sympathetic nerve activity (MSNA), femoral artery blood flow, and femoral artery conductance (Doppler ultrasound) were quantified in eight men (27 ± 4 yr) and nine women (28 ± 4 yr) before [control (CON)], during (INF), and immediately after (post-INF) a local infusion of saline [5% of the total forearm volume (30 ml/min); the infusion time was 2 ± 1 and 1 ± 1 min ( P = 0.0001) for men and women, respectively] through a retrograde catheter inserted into an antecubital vein, to which venous drainage and arterial supply had been occluded. Mean arterial pressure increased during and after infusion in both groups (vs. the CON group, P < 0.05), but women showed a smaller pressor response in the post-INF period (Δ+7.2 ± 2.0 vs. Δ+18.3 ± 3.9 mmHg in men, P = 0.019). MSNA increased and femoral artery conductance decreased similarly in both groups (vs. the CON group, P < 0.05) at post-INF. Although HR changes were similar, increases in SV (Δ+20.4 ± 8.6 vs. Δ+2.6 ± 2.7 ml, P = 0.05) and CO (Δ+0.84 ± 0.17 vs. Δ+0.34 ± 0.10 l/min, P = 0.024) were greater in men compared with women. Therefore, venous distension evokes a smaller pressor response in young women due to attenuated cardiac adjustments rather than reduced venous compliance or sympathetic transduction. NEW & NOTEWORTHY We found that the pressor response to venous distension was attenuated in young women compared with age-matched men. This was due to attenuated cardiac adjustments rather than reduced venous compliance, sympathetic activation, or impaired transduction and vascular control. Collectively, these findings suggest that an attenuated venous distension reflex could be involved in orthostatic intolerance in young women.
Assuntos
Hemodinâmica/fisiologia , Músculo Liso Vascular/fisiologia , Sistema Nervoso Simpático/fisiologia , Adulto , Pressão Arterial/fisiologia , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiologia , Antebraço/irrigação sanguínea , Humanos , Hipotensão Ortostática/fisiopatologia , Masculino , Músculo Liso Vascular/inervação , Estimulação Física , Fluxo Sanguíneo Regional/fisiologia , Células Receptoras Sensoriais/fisiologia , Caracteres Sexuais , Resistência Vascular , Adulto JovemRESUMO
OBJECTIVE: Describir el papel de la percepción del gusto como factor de riesgo para el desarrollo de obesidad en niños. MATERIALS AND METHODS: ulos científicos publicados en PubMed entre el 1 de enero de 2011 y el 20 de marzo de 2016 para el tema sobrepeso y obesidad en niños de entre 0 y 12 años. Los algoritmos utilizados fueron (Obesity OR Overweight) AND Taste perception, Satiation, Satiety response, Appetite, Appetite regulation, Habituation, Taste receptors [MeSH] y PROP phenotype. En búsquedas subsecuentes se incluyeron artículos previos y posteriores a la fecha de la búsqueda general (hasta mayo 2018). RESULTS: Las preferencias por los sabores inician desde la gestación, por lo que los niños que son expuestos a sabores dulces en etapas tempranas de la infancia aumentan su riesgo de habituación a éstos. Asimismo, las experiencias hedónicas dadas por la ingestión de alimentos y bebidas dulces refuerzan el consumo de estos alimentos, lo que propicia la selección de productos o bebidas de sabor dulce en etapas posteriores. Estas preferencias se han asociado con el desarrollo de obesidad en los niños. Las variantes genéticas relacionadas con la percepción del gusto también pueden contribuir a la selección de cierto tipo de alimentos. Sin embargo, su relación con una mayor ingestión de energía, así como con un mayor peso corporal, ha sido poco explorada y ha mostrado resultados inconsistentes. CONCLUSIONS: Se requiere más evidencia para entender las interacciones ambientales y genéticas de la percepción del gusto, a fin de considerarlo un factor más en las intervenciones de política pública.
Assuntos
Preferências Alimentares , Obesidade Infantil/epidemiologia , Percepção Gustatória , Criança , Pré-Escolar , Ingestão de Energia , Comportamento Alimentar , Feminino , Habituação Psicofisiológica , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade Infantil/etiologia , Obesidade Infantil/psicologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco , Resposta de Saciedade , Células Receptoras Sensoriais/fisiologiaRESUMO
Resumen Objetivo Describir el papel de la percepción del gusto como factor de riesgo para el desarrollo de obesidad en niños. Material y métodos Se realizó una búsqueda inicial de artículos científicos publicados en PubMed entre el 1 de enero de 2011 y el 20 de marzo de 2016 para el tema sobrepeso y obesidad en niños de entre 0 y 12 años. Los algoritmos utilizados fueron (Obesity OR Overweight) AND Taste perception, Satiation, Satiety response, Appetite, Appetite regulation, Habituation, Taste receptors [MeSH] y PROP phenotype. En búsquedas subsecuentes se incluyeron artículos previos y posteriores a la fecha de la búsqueda general (hasta mayo 2018). Resultados Las preferencias por los sabores inician desde la gestación, por lo que los niños que son expuestos a sabores dulces en etapas tempranas de la infancia aumentan su riesgo de habituación a éstos. Asimismo, las experiencias hedónicas dadas por la ingestión de alimentos y bebidas dulces refuerzan el consumo de estos alimentos, lo que propicia la selección de productos o bebidas de sabor dulce en etapas posteriores. Estas preferencias se han asociado con el desarrollo de obesidad en los niños. Las variantes genéticas relacionadas con la percepción del gusto también pueden contribuir a la selección de cierto tipo de alimentos. Sin embargo, su relación con una mayor ingestión de energía, así como con un mayor peso corporal, ha sido poco explorada y ha mostrado resultados inconsistentes. Conclusiones Se requiere más evidencia para entender las interacciones ambientales y genéticas de la percepción del gusto, a fin de considerarlo un factor más en las intervenciones de política pública.
Abstract Objective To describe the role of taste perception in the development of sweet taste habituation as well as its relationship to the development of obesity in children. Materials and methods An initial search of scientific articles published in PubMed between January 1st, 2011 and March 20th, 2016 was performed in children between 0 and 12 years old. The algorithms used were (Obesity OR Overweight) AND (Taste perception, Satiation, Satiety response, Appetite, Appetite regulation Habituation, Taste receptors [MeSH]) and PROP phenotype. Subsequent searches included papers published before and after date of initial search (until May 2018). Results Flavor preferences start as early as taste system development during pregnancy. Therefore, children who are exposed to sweet flavors in early childhood, increase their risk of habituation to them. Likewise, the hedonic experiences given by the ingestion of sweet foods and beverages, reinforce the consumption of these foods, perpetuating their selection in later stages. Preference for sweet taste has been associated with the development of obesity in children. Functional genetic variants related to taste perception can also contribute to the selection of certain types of foods and there is enough evidence that supports this idea. However, its contribution to a higher energy intake as well as a higher body weight has been poorly explored with inconsistent results. Conclusions More evidence is required to understand the environmental and genetic interactions of taste perception, so in turn, it can be consider as a key factor for preventing child obesity.