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1.
Pflugers Arch ; 475(2): 233-248, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36289078

RESUMO

One side effect of cisplatin, a cytotoxic platinum anticancer drug, is peripheral neuropathy; however, its central nervous system effects remain unclear. We monitored respiratory nerve activity from the C4 ventral root in brainstem and spinal cord preparations from neonatal rats (P0-3) to investigate its central effects. Bath application of 10-100 µM cisplatin for 15-20 min dose-dependently decreased the respiratory rate and increased the amplitude of C4 inspiratory activity. These effects were not reversed after washout. In separate perfusion experiments, cisplatin application to the medulla decreased the respiratory rate, and application to the spinal cord increased the C4 burst amplitude without changing the burst rate. Application of other platinum drugs, carboplatin or oxaliplatin, induced no change of respiratory activity. A membrane potential analysis of respiratory-related neurons in the rostral medulla showed that firing frequencies of action potentials in the burst phase tended to decrease during cisplatin application. In contrast, in inspiratory spinal motor neurons, cisplatin application increased the peak firing frequency of action potentials during the inspiratory burst phase. The increased burst amplitude and decreased respiratory frequency were partially antagonized by riluzole and picrotoxin, respectively. Taken together, cisplatin inhibited respiratory rhythm via medullary inhibitory system activation and enhanced inspiratory motor nerve activity by changing the firing property of motor neurons.


Assuntos
Cisplatino , Taxa Respiratória , Ratos , Animais , Animais Recém-Nascidos , Cisplatino/farmacologia , Ratos Wistar , Platina , Bulbo/fisiologia , Medula Espinal , Neurônios Motores , Respiração
2.
Pflugers Arch ; 475(11): 1301-1314, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37707585

RESUMO

Aconitine is a sodium channel opener, but its effects on the respiratory center are not well understood. We investigated the dose-dependent effects of aconitine on central respiratory activity in brainstem-spinal cord preparations isolated from newborn rats. Bath application of 0.5-5 µM aconitine caused an increase in respiratory rhythm and decrease in the inspiratory burst amplitude of the fourth cervical ventral root (C4). Separate application of aconitine revealed that medullary neurons were responsible for the respiratory rhythm increase, and neurons in both the medulla and spinal cord were involved in the decrease of C4 amplitude by aconitine. A local anesthetic, lidocaine (100 µM), or a voltage-dependent sodium channel blocker, tetrodotoxin (0.1 µM), partially antagonized the C4 amplitude decrease by aconitine. Tetrodotoxin treatment tentatively decreased the respiratory rhythm, but lidocaine tended to further increase the rhythm. Treatment with 100 µM riluzole or 100 µM flufenamic acid, which are known to inhibit respiratory pacemaker activity, did not reduce the respiratory rhythm enhanced by aconitine + lidocaine. The application of 1 µM aconitine depolarized the preinspiratory, expiratory, and inspiratory motor neurons. The facilitated burst rhythm of inspiratory neurons after aconitine disappeared in a low Ca2+/high Mg2+ synaptic blockade solution. We showed the dose-dependent effects of aconitine on respiratory activity. The antagonists reversed the depressive effects of aconitine in different manners, possibly due to their actions on different sites of sodium channels. The burst-generating pacemaker properties of neurons may not be involved in the generation of the facilitated rhythm after aconitine treatment.


Assuntos
Aconitina , Tronco Encefálico , Animais , Ratos , Animais Recém-Nascidos , Aconitina/farmacologia , Tetrodotoxina/farmacologia , Ratos Wistar , Bulbo/fisiologia , Medula Espinal , Lidocaína/farmacologia
3.
J Therm Biol ; 113: 103543, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37055119

RESUMO

Maintenance of body temperature (Tb) at various ambient temperatures (Ta) during fasting is important for homeotherms. Fasting decreases Tb in thermoneutral and cold conditions and facilitates thermoregulatory behavior in the cold in rats; however, the mechanism is unknown. We focused on ghrelin, a hormone secreted by the stomach during fasting, in two circulatory forms: acyl ghrelin (AG) and des-acyl ghrelin (DAG). AG is called active ghrelin, while DAG, the non-active ghrelin, was unknown for a long time before its many functions were recently clarified. In the present review, we present the modulation of AG and DAG on autonomic and behavioral thermoregulation at various Ta and discuss the differences between their modulation on thermoregulation. AG decreases Tb in thermoneutral and cold conditions but does not affect the thermoregulatory behavior of rodents in cold conditions. The DAG decreases Tb in thermoneutral and hot conditions, but it does not affect Tb and facilitates the thermoregulatory behavior of rodents in the cold. These findings indicate that the actions of AG and DAG on thermoregulation are similar in thermoneutral conditions but are different in cold conditions.


Assuntos
Regulação da Temperatura Corporal , Grelina , Ratos , Animais , Temperatura , Temperatura Corporal
4.
Circ J ; 86(5): 787-796, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35153272

RESUMO

BACKGROUND: The long-term safety and utility of intravascular ultrasound (IVUS)-guided zero-contrast percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD) are unknown.Methods and Results: A total of 698 consecutive patients treated with PCI (1,061 procedures) in our center were studied. Patients with acute coronary syndrome, who are on maintenance hemodialysis, and who had a planned rotational atherectomy were excluded. Finally, they were divided into 2 groups: zero-contrast PCI (n=55, 78 procedures) and conventional PCI (n=462, 670 procedures). After propensity score matching, 50 patients were matched for each group to evaluate long-term outcomes. Primary endpoints were major adverse cardiovascular events (MACE), including all-cause death, non-fatal myocardial infarction (MI), and clinically driven target lesion revascularization. All patients in the zero-contrast PCI group had stage 3-5 CKD with an estimated glomerular filtration rate of 38.3±14.8 mL/min/1.73 m2. Zero-contrast PCI was successful in all 78 procedures without renal events such as acute kidney injury or emergent hemodialysis and procedural complications such as coronary perforation or periprocedural MI. During a follow-up period of 32 months, 7 patients died (1 cardiac, 6 non-cardiovascular), and 4 patients were introduced to renal replacement therapy. The incidence of MACE was similar between the zero-contrast and conventional PCI groups (log-rank, P=0.95). CONCLUSIONS: IVUS-guided zero-contrast PCI might be safe and feasible in patients with CKD with satisfactory acute and long-term renal and cardiovascular outcomes.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
5.
J Therm Biol ; 108: 103290, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36031211

RESUMO

The basal body temperature (BBT) in women is biphasic, with high- and low-temperature phases during the menstrual cycle. Biphasic BBT predicts the date of ovulation for contraception and family planning. Although the BBT is measured with a basal thermometer at rest, upon waking up, it is often tedious to measure for women. Additionally, the single measured values are not sufficient to reflect biphasic BBT. To solve these problems, various wearable devices have been developed. In the present review, we introduce these devices, compare them to other available basal thermometers, and discuss possible future devices. Wearable devices used to measure skin temperature, ear canal temperature, and temperature in clothes during nighttime to predict BBT (the type of bracelet, ring, armband, ear, and waist), have been developed. These devices are convenient for users, because they measure and record temperature automatically during the nighttime instead of every morning. The scientific evidence was most documented for the type of bracelet, wherein the wrist skin temperature measured during the nighttime reflected the biphasic BBT and predicted the date of ovulation. The popular wearable device, FitbitⓇ measures the wrist skin temperature; in addition, the recent patent information states that the Apple WatchⓇ might have added the same function. Although there have been no previous studies, these devices might reflect biphasic BBT, because they are similar to bracelets. These devices are popular in the healthcare market; therefore, their function to measure wrist skin temperature may supplant other devices to predict the date of ovulation in the future.


Assuntos
Temperatura Corporal , Dispositivos Eletrônicos Vestíveis , Feminino , Humanos , Ciclo Menstrual , Ovulação , Termômetros
6.
J Neurosci Res ; 99(5): 1325-1336, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33594677

RESUMO

Parkinson's disease (PD) impairs various cognitive functions, including time perception. Dysfunctional time perception in PD is poorly understood, and no study has investigated the rehabilitation of time perception in patients with PD. We aimed to induce the recovery of time perception in PD patients and investigated the potential relationship between recovery and cognitive functions/domains other than time perception. Sixty patients with PD (27 females) and 20 healthy controls (10 females) were recruited. The participants underwent a feedback training protocol for 4 weeks to improve the accuracy of subjective spatial distance or time duration using a ruler or stopwatch, respectively. They participated in three tests at weekly intervals, each comprising 10 types of cognitive tasks and assessments. After duration feedback training for 1 month, performance on the Go/No-go task, Stroop task, and impulsivity assessment improved in patients with PD, while no effect was observed after distance feedback training. Additionally, the effect of training on duration production correlated with extended reaction time and improved accuracy in the Go/No-go and Stroop tasks. These findings suggest that time perception is functionally linked to inhibitory systems. If the feedback training protocol can modulate and maintain time perception, it may improve various cognitive/psychiatric functions in patients with PD. It may also be useful in the treatment of diseases other than PD that cause dysfunctions in temporal processing.


Assuntos
Cognição/fisiologia , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Tempo de Reação/fisiologia , Percepção Espacial/fisiologia , Percepção do Tempo/fisiologia , Estimulação Acústica/métodos , Idoso , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Distribuição Aleatória
7.
BMC Neurosci ; 22(1): 75, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876001

RESUMO

BACKGROUND: Cognitive function declines with age and has been shown to be associated with atrophy in some brain regions, including the prefrontal cortex. However, the details of the relationship between aging and cognitive dysfunction are not well understood. METHODS: Across a wide range of ages (24- to 85-years-old), this research measured the gray matter volume of structural magnetic resonance imaging data in 39 participants, while some brain regions were set as mediator variables to assess the cascade process between aging and cognitive dysfunction in a path analysis. RESULTS: Path analysis showed that age affected the left hippocampus, thereby directly affecting the left superior frontal gyrus. Furthermore, the gyrus directly affected higher order flexibility and maintenance abilities calculated as in the Wisconsin card sorting test, and the two abilities affected the assessment of general cognitive function. CONCLUSION: Our finding suggests that a cascade process mediated by the left hippocampus and left superior frontal gyrus is involved in the relationship between aging and cognitive dysfunction.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Hipocampo/patologia , Lobo Temporal/patologia , Adulto , Idoso , Envelhecimento/fisiologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/patologia , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Temporal/fisiopatologia , Adulto Jovem
8.
J Therm Biol ; 100: 103029, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34503776

RESUMO

Thermoregulation is crucial for human survival at various ambient temperatures. Transient receptor potential (TRP) and TWIK-related K+ (TREK) channels expressed in sensory neurons play a role in peripheral thermosensitivity for temperature detection. In addition, these channels have various physiological roles in the skeletal, nervous, immune, vascular, digestive, and urinary systems. In women, the female hormones estradiol (E2) and progesterone (P4), which fluctuate during the menstrual cycle, affect various physiological functions, such as thermoregulation in hot and cold environments. The present review describes the effect of female hormones on TRP and TREK channels and related physiological functions. The P4 decreased thermosensitivity via TRPV1. E2 facilitates temporomandibular joint disease (TRPV1), breast cancer (TRPM8), and calcium absorption in the digestive system (TRPV5 and TRPV6), inhibits the facilitation of vasoconstriction (TRPM3), nerve inflammation (TRPM4), sweetness sensitivity (TRPM5), and menstrual disorders (TRPC1), and prevents insulin resistance (TRPC5) via each channel. P4 inhibits vasoconstriction (TRPM3), sweetness sensitivity (TRPM5), ciliary motility in the lungs (TRPV4), menstrual disorder (TRPC1), and immunity (TRPC3), and facilitates breast cancer (TRPV6) via each channel as indicated. The effects of female hormones on TREK channels and physiological functions are still under investigation. In summary, female hormones influence physiological functions via some TRP channels; however, the literature is not comprehensive and future studies are needed, especially those related to thermoregulation in women.


Assuntos
Estradiol/metabolismo , Ciclo Menstrual , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Progesterona/metabolismo , Sensação Térmica , Canais de Potencial de Receptor Transitório/metabolismo , Feminino , Humanos
9.
Pflugers Arch ; 471(11-12): 1419-1439, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31631251

RESUMO

Paired-like homeobox gene Phox2b is predominantly expressed in pre-inspiratory neurons in the parafacial respiratory group (pFRG) in newborn rat rostral ventrolateral medulla. To analyse detailed local networks of the respiratory centre using optogenetics, the effects of selective activation of Phox2b-positive neurons in the ventral medulla on respiratory rhythm generation were examined in brainstem-spinal cord preparations isolated from transgenic newborn rats with Phox2b-positive cells expressing channelrhodopsin variant ChRFR(C167A). Photostimulation up to 43 s increased the respiratory rate > 200% of control, whereas short photostimulation (1.5 s) of the rostral pFRG reset the respiratory rhythm. At the cellular level, photostimulation depolarised Phox2b-positive pre-inspiratory, inspiratory and respiratory-modulated tonic neurons and Phox2b-negative pre-inspiratory neurons. In contrast, changes in membrane potential of Phox2b-negative inspiratory and expiratory neurons varied depending on characteristics of ongoing synaptic connections in local respiratory networks in the rostral medulla. In the presence of tetrodotoxin, photostimulation depolarised Phox2b-positive cells, but caused no significant changes in membrane potential of Phox2b-negative cells. We concluded that depolarisation of Phox2b-positive neurons was due to cell-autonomous photo-activation and summation of excitatory postsynaptic potentials, whereas membrane potential changes of Phox2b-negative neurons depended on the network configuration. Our findings shed further light on local networks among respiratory-related neurons in the rostral ventrolateral medulla and emphasise the important role of pre-inspiratory neurons in respiratory rhythm generation in the neonatal rat en bloc preparation.


Assuntos
Channelrhodopsins/metabolismo , Proteínas de Homeodomínio/metabolismo , Bulbo/metabolismo , Neurônios/metabolismo , Centro Respiratório/metabolismo , Fatores de Transcrição/metabolismo , Animais , Animais Recém-Nascidos , Tronco Encefálico/metabolismo , Feminino , Masculino , Potenciais da Membrana/fisiologia , Optogenética/métodos , Ratos , Respiração , Tetrodotoxina/metabolismo
11.
Pflugers Arch ; 470(2): 385-394, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28963585

RESUMO

Eugenol is contained in several plants including clove and is used as an analgesic drug. In the peripheral and central nervous systems, this compound modulates neuronal activity through action on voltage-gated ionic channels and/or transient receptor potential channels. However, it is unknown whether eugenol exerts any effects on the respiratory center neurons in the medulla. We examined the effects of eugenol on respiratory rhythm generation in the brainstem-spinal cord preparation from newborn rat (P0-P3). The preparations were superfused by artificial cerebrospinal fluid at 25-26 °C, and inspiratory C4 ventral root activity was monitored. Membrane potentials of respiratory neurons were recorded in the parafacial region of the rostral ventrolateral medulla. Bath application of eugenol (0.5-1 mM) decreased respiratory rhythm accompanied by strong inhibition of the burst activity of pre-inspiratory neurons. After washout, respiratory rhythm partly recovered, but the inspiratory burst duration was extremely shortened, and this continued for more than 60 min after washout. The shortening of C4 inspiratory burst by eugenol was not reversed by capsazepine (TRPV1 antagonist) or HC-030031 (TRPA1 antagonist), whereas the depression was partially blocked by GABAA antagonist bicuculline and glycine antagonist strychnine or GABAB antagonist phaclofen. A spike train of action potentials in respiratory neurons induced by depolarizing current pulse was depressed by application of eugenol. Eugenol decreased the negative slope conductance of pre-inspiratory neurons, suggesting blockade of persistent Na+ current. These results suggest that changes in both membrane excitability and synaptic connections are involved in the shortening of respiratory neuron bursts by eugenol.


Assuntos
Potenciais de Ação , Tronco Encefálico/fisiologia , Eugenol/farmacologia , Respiração , Medula Espinal/fisiologia , Acetanilidas/farmacologia , Animais , Tronco Encefálico/citologia , Tronco Encefálico/efeitos dos fármacos , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Purinas/farmacologia , Ratos , Ratos Wistar , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/antagonistas & inibidores
12.
Exp Brain Res ; 236(6): 1767-1774, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29654351

RESUMO

Eugenol is contained in several plants including clove and is thought to exert an analgesic effect. It has been suggested that the slow ventral root potential induced by ipsilateral dorsal root stimulation in the isolated (typically lumbar) spinal cord of newborn rats reflects the nociceptive response, and this in vitro experimental model is useful to assess the actions of analgesics. To further elucidate neuronal mechanisms of eugenol-induced analgesia, we examined the effects of extracellularly applied eugenol on the nociceptive spinal reflex response. To evaluate the effects of eugenol on putative nociceptive responses, the ipsilateral fifth lumbar (L5) dorsal root was stimulated using a glass suction electrode, and the induced reflex responses were recorded from the L5 and twelfth thoracic (Th12) ventral roots in spinal cord preparations (Th10-L5) from newborn rats (postnatal day 0-3). We found that eugenol (0.25-1.0 mM) caused dose-dependent attenuation of the reflex response and also depressed spontaneous ventral root activity. We also found that the slow ventral root potential was further divided into two components: initial and late components. A lower concentration of eugenol selectively depressed the late component. The inhibitory effects by 1.0 mM eugenol were not reversed by 10 µM capsazepine (TRPV1 antagonist) or 40 µM HC-030031 (TRPA1 antagonist). The depressive effect of eugenol on the reflex response was also confirmed by optical recordings using voltage-sensitive dye. Our report provides additional evidence on the basic neuronal mechanisms of eugenol to support its clinical use as a potential analgesic treatment.


Assuntos
Analgésicos/farmacologia , Eugenol/farmacologia , Potenciais Evocados/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Raízes Nervosas Espinhais/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Estimulação Elétrica , Imagem Óptica , Ratos , Ratos Wistar
13.
Exp Brain Res ; 232(7): 2197-206, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24671653

RESUMO

There is some evidence that signals coming from both arms are used to determine the perceived position and movement of one arm. We examined whether the sense of position and movement of one (reference) arm is altered by increases in muscle spindle signals in the other (indicator) arm in blindfolded participants (n = 26). To increase muscle spindle discharge, we applied 70-80 Hz muscle vibration to the elbow flexors of the indicator arm. In a first experiment, proprioceptive illusions in the vibrated reference arm in a forearm position-matching task were compared between conditions in which the indicator arm elbow flexors were vibrated or not vibrated. We found that the vibration illusion of arm extension induced by vibration of reference arm elbow flexors was reduced in the presence of vibration of the indicator elbow flexors. In a second experiment, participants were asked to describe their perception of the illusion of forearm extension movements of the reference arm evoked by vibration of reference arm elbow flexors in response to on/off and off/on transitions of vibration of non-reference arm elbow flexors. When vibration of non-reference arm elbow flexors was turned on, they reported a sensation of slowing down of the illusion of the reference arm. When it was turned off, they reported a sensation of speeding up. To conclude, the present study shows that both the sense of limb position and the sense of limb movement of one arm are dependent to some extent on spindle signals coming from the other arm.


Assuntos
Braço/inervação , Lateralidade Funcional/fisiologia , Ilusões/fisiologia , Propriocepção/fisiologia , Vibração , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Estimulação Física , Fatores de Tempo
14.
PLoS One ; 19(4): e0301543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557587

RESUMO

This study aimed to explore the relationship between gray matter volume changes and various clinical parameters in patients with migraine, focusing on symptom severity, quality of life, and states of depression and anxiety. Using a case-control design, we examined 33 patients with migraine, with or without aura, and 27 age-matched healthy subjects. We used magnetic resonance imaging to assess the volumes of 140 bilateral brain regions. Clinical evaluations included the Migraine Disability Assessment, the Migraine Specific Quality of Life Questionnaire, the Center for Epidemiologic Studies Depression scale, Spielberger's State and Trait Anxiety scales, and the Japanese version of the Montreal Cognitive Assessment. We compared the scores of these measures between migraine patients and healthy controls to examine the interplay between brain structure and clinical symptoms. Significant volumetric differences were observed in the pallidum and amygdala between migraine patients and healthy individuals. The reduction in the right amygdala volume correlated significantly with migraine severity as measured by the Migraine Disability Assessment. Path analysis revealed a model where Migraine Disability Assessment scores were influenced by Migraine Specific Quality of Life Questionnaire outcomes, which were further affected by depression, anxiety, and a low right pallidum volume. Our findings suggest that the chronicity and severity of migraine headaches specifically affect the right amygdala. Our path model suggests a complex relationship whereby migraine disability is strongly influenced by quality of life, which is, in turn, affected by psychological states, such as anxiety and depression.


Assuntos
Transtornos de Enxaqueca , Enxaqueca com Aura , Humanos , Qualidade de Vida , Transtornos de Enxaqueca/diagnóstico , Encéfalo , Ansiedade , Imageamento por Ressonância Magnética
15.
Exp Physiol ; 98(2): 491-500, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23024370

RESUMO

Previously, we undertook simultaneous recording of ventilation and pulmonary gas exchange in mice and revealed that dopamine D(2) receptors participate in exercise hyperpnoea via behavioural control of ventilation with unchanged pulmonary gas exchange. Here, we examined the hypothesis that D(1) receptors also contribute to exercise hyperpnoea using a D(1) receptor antagonist (SCH 23390; SCH) that crosses the blood-brain barrier, with the same recording technique and protocol as in the previous study. The respiratory responses of mice injected with saline or SCH (50 µg (kg body weight)(-1), i.p.) were compared during constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber equipped with a differential pressure transducer and open-circuit system with a mass spectrometer. At rest, SCH-injected mice had significantly reduced respiratory frequency, minute ventilation and pulmonary gas exchange compared with saline-injected mice. Ventilation during hyperoxic gas inhalation and hypercapnic ventilatory responses between groups were similar. Abrupt increases and sequential declines to the steady-state level were produced by treadmill exercise in both groups of mice. Treatment with SCH lowered the increased levels of respiratory frequency, tidal volume and minute ventilation during the steady state, as well as reducing the O(2) uptake, CO(2) output and body temperature throughout treadmill exercise. These data suggest that D(1) receptors contribute to a resting ventilation level and exercise hyperpnoea during the steady state in parallel with metabolic changes. Notably, the metabolic control of D(1) receptors was important for maintenance of the steady state, and D(1) receptors in hypothalamic nuclei could be involved in this modulation.


Assuntos
Encéfalo/metabolismo , Hipercapnia/etiologia , Pulmão/fisiopatologia , Esforço Físico , Troca Gasosa Pulmonar , Ventilação Pulmonar , Receptores de Dopamina D1/metabolismo , Animais , Benzazepinas/administração & dosagem , Benzazepinas/metabolismo , Barreira Hematoencefálica/metabolismo , Regulação da Temperatura Corporal , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Permeabilidade Capilar , Modelos Animais de Doenças , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/metabolismo , Hipercapnia/metabolismo , Hipercapnia/fisiopatologia , Injeções Intraperitoneais , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Troca Gasosa Pulmonar/efeitos dos fármacos , Ventilação Pulmonar/efeitos dos fármacos , Receptores de Dopamina D1/antagonistas & inibidores , Corrida , Fatores de Tempo
16.
J Physiol Sci ; 73(1): 23, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803279

RESUMO

A metabolite of acetaminophen, AM404, which is an anandamide transporter inhibitor, induces analgesia mainly via activation of transient receptor potential channel 1 in the spinal cord, although the role of cannabinoid receptors remains to be studied. The ventral root reflex response induced by stimulation of the dorsal root in in vitro preparations of rat spinal cord is useful to assess the effect of analgesics. We analyzed the effects of AM404 and cannabinoid receptor antagonist AM251 on reflex responses in lumbar spinal cord preparations from newborn rats and found that the amplitude of the slow ventral root potential after administration of 10 µM AM404 was not significantly changed, whereas 10 µM AM251 significantly increased the amplitude. Administration of the cannabinoid receptor 1 agonist WIN55,212-2 (10 µM) did not significantly affect the reflex response. We suggest that endogenous cannabinoids in the spinal cord are involved in the antinociceptive mechanism through suppressive effects.


Assuntos
Nociceptividade , Medula Espinal , Ratos , Animais , Animais Recém-Nascidos , Ratos Wistar , Receptores de Canabinoides/metabolismo
17.
Respir Physiol Neurobiol ; 318: 104163, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37734454

RESUMO

This study aimed to clarify the differential exercise capacity between 2-month-old and 10-month-old mice using an incremental running test. Metabolic and ventilatory responses and blood lactate concentration were measured to evaluate exercise capacity. We examined whether incremental running test results reflected metabolic and ventilatory responses and blood lactate concentration observed during the steady-state running test. Metabolic response significantly declined with age, whereas ventilatory response was similar between the groups. A low-intensity/moderate exercise load of 10/min in an incremental running test was performed on both mice for 30 min. They showed a characteristic pattern in ventilatory response in 10-month mice. The results of incremental running tests didn't necessarily reflect the steady-state metabolic and ventilatory responses because some parameters showed an approximation and others did not in incremental and steady-state tests, which changed with age. Our study suggests metabolic and ventilatory responses depending on age and provides basic knowledge regarding the objective and quantitative assessment of treadmill running in an animal model.

18.
Neuroscience ; 528: 89-101, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37557948

RESUMO

Proteinase-activated receptor-1 (PAR1) is expressed in astrocytes of various brain regions, and its activation is involved in the modulation of neuronal activity. Here, we report effects of PAR1 selective agonist TFLLR on respiratory rhythm generation in brainstem-spinal cord preparations. Preparations were isolated from newborn rats (P0-P4) under deep isoflurane anesthesia and were transversely cut at the rostral medulla. Preparations were superfused with artificial cerebrospinal fluid (25-26 °C), and inspiratory C4 ventral root activity was monitored. The responses to TFLLR of cells close to the cut surface were detected by calcium imaging or membrane potential recordings. Application of 10 µM TFLLR (4 min) induced a rapid and transient increase of calcium signal in cells of the ventrolateral respiratory regions of the medulla. More than 88% of responding cells (223/254 cells from 13 preparations) were also activated by low (0.2 mM) K+ solution, suggesting that they were astrocytes. Immunohistochemical examination demonstrated that PAR1 was expressed on many astrocytes. Respiratory-related neurons in the medulla were transiently hyperpolarized (-1.8 mV) during 10 µM TFLLR application, followed by weak membrane depolarization after washout. C4 burst rate decreased transiently in response to application of TFLLR, followed by a slight increase. The inhibitory effect was partially blocked by 50 µM theophylline. In conclusion, activation of astrocytes via PAR1 resulted in a decrease of inspiratory C4 burst rate in association with transient hyperpolarization of respiratory-related neurons. After washout, slow and weak excitatory responses appeared. Adenosine may be partially involved in the inhibitory effect of PAR1 activation.


Assuntos
Cálcio , Receptor PAR-1 , Animais , Ratos , Animais Recém-Nascidos , Ratos Wistar , Tronco Encefálico/fisiologia , Bulbo , Medula Espinal
19.
Biomed Res ; 44(2): 41-49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37005282

RESUMO

Seizure-like burst activities are induced by blockade of GABAA and/or glycine receptors in various spinal ventral roots of brainstem-spinal cord preparation from neonatal rodents. We found that this is not applicable to the phrenic nerve and that a new inhibitory descending pathway may suppress seizure-like activity in the phrenic nerve. Experiments were performed in brainstem-spinal cord preparation from newborn rats (age: 0-1 day). Left phrenic nerve and right C4 activities were recorded simultaneously. When GABAA and glycine receptors were blocked by 10 µM bicuculline and 10 µM strychnine (Bic+Str), seizure-like burst activities appeared in the fourth cervical ventral root (C4) but not the phrenic nerve. After making a transverse section at C1, the inspiratory burst activity disappeared from both C4 and the phrenic nerve, whereas seizure-like activity appeared in both nerves. We hypothesized that inhibitory descending pathways other than those via GABAA and/or glycine receptors (from the medulla to the spinal cord) work to avoid disturbance of regular respiratory-related diaphragm contraction by seizure-like activity. We found that cannabinoid receptor antagonist, AM251 was effective for the induction of seizure-like activity by Bic+Str in the phrenic nerve in brainstem-spinal cord preparation. Cannabinoid receptors may be involved in this descending inhibitory system.


Assuntos
Receptores de Glicina , Medula Espinal , Animais , Ratos , Animais Recém-Nascidos , Receptores de Canabinoides , Bicuculina/farmacologia , Estricnina/farmacologia , Convulsões/tratamento farmacológico , Nervo Frênico/fisiologia
20.
Sci Rep ; 13(1): 920, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650347

RESUMO

Change in body perception requires recalibration of various sensory inputs. However, it is less known how information other than sensations relates to the recalibration of body perception. Here, we focused on the relationship between respiration and cognition and investigated whether respiratory rhythms are related to the recalibration of hand perception. We built a visual feedback environment, in which a mannequin hand moved in conjunction with its own respiratory rhythm, and participants performed an experiment under conditions in congruency/incongruency for spatial and temporal factors. The temporal and spatial congruency between own respiratory rhythm and the mannequin hand markedly facilitated the phenomenon of hand ownership sense transfer to the mannequin hand, while incongruency had little effect on the change in hand ownership. The finding suggests that an internal model in the brain allows respiratory rhythms to be involved in the adaptation of the body's neural representations.


Assuntos
Ilusões , Percepção Visual , Humanos , Encéfalo , Cognição , Mãos , Respiração
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