Journal of Physiological Sciences最新文献

An increase in ambient temperature leads to an increase in sleep. However, the mechanisms behind this phenomenon remain unknown. This study aimed to investigate the role of microglia in the increase of sleep caused by high ambient temperature. We confirmed that at 35 °C, slow-wave sleep was significantly increased relative to those observed at 25 °C. Notably, this effect was abolished upon treatment with PLX3397, a CSF1R inhibitor that can deplete microglia, while sleep amount at 25°C was unaffected. These observations suggest that microglia play a pivotal role in modulating the homeostatic regulation of sleep in response to the fluctuations in ambient temperature.

The joint workshop between U.S. and Japanese researchers, supported by The U.S.-Japan Brain Research Cooperative Program, convened in January 2023 at Keio University Mita campus in Tokyo, Japan. The workshop had a threefold objective. Firstly, it aimed to facilitate robust exchanges between U.S. and Japanese researchers engaged in Neurovascular Unit (NVU) research, enhancing the global network of scholars in the field. Secondly, it aimed to encourage the initiation of collaborative research projects, fostering interdisciplinary efforts and synergistic advancements in understanding the brain vascular physiology and central nervous system. Lastly, the workshop emphasized the nurturing of young researchers, recognizing their pivotal role in shaping the future of NVU research. Throughout the workshop, participants discussed fundamental aspects of the NVU, exploring its complex connections and vital functions. By sharing their expertise and insights, the workshop attendees sought to uncover novel approaches to mitigate the burden of neurological diseases for individuals worldwide. This report provides a summary of the presentations and discussions held during the workshop, showcasing the collective efforts and progress made by the participants.

Previously, we found that serotonin (5-HT) release in the central nucleus of the amygdala (CeA) of anesthetized rats decreases in response to innocuous stroking of the skin, irrespective of stimulus laterality, but increases in response to noxious pinching applied to a hindlimb contralateral to the 5-HT measurement site. The aim of the present study was to determine whether intra-CeA 5-HT release responses to cutaneous stimulation were altered in an animal model of neuropathic pain induced by ligation of the left L5 spinal nerve. In anesthetized neuropathic pain model rats, stroking of the left hindlimb increased 5-HT release in the CeA, whereas stroking of the right hindlimb decreased it. Meanwhile, pinching of the left hindlimb increased intra-CeA 5-HT release irrespective of stimulus laterality. In conclusion, the present study demonstrated that intra-CeA 5-HT release responses to cutaneous stimulation are altered in an animal model of neuropathic pain.

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure-volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator.

Plasticity is a common feature of synapses that is stated in different ways and occurs through several mechanisms. The regular action of the brain needs to be balanced in several neuronal and synaptic features, one of which is synaptic plasticity. The different homeostatic processes, including the balance between excitation/inhibition or homeostasis of synaptic weights at the single-neuron level, may obtain this. Homosynaptic Hebbian-type plasticity causes associative alterations of synapses. Both homosynaptic and heterosynaptic plasticity characterize the corresponding aspects of adjustable synapses, and both are essential for the regular action of neural systems and their plastic synapses.In this review, we will compare homo- and heterosynaptic plasticity and the main factors affecting the direction of plastic changes. This review paper will also discuss the diverse functions of the different kinds of heterosynaptic plasticity and their properties. We argue that a complementary system of heterosynaptic plasticity demonstrates an essential cellular constituent for homeostatic modulation of synaptic weights and neuronal activity.

This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

Physiological roles of Cl^-, a major anion in the body, are not well known compared with those of cations. This review article introduces: (1) roles of Cl^- in bodily and cellular functions; (2) the range of cytosolic Cl^- concentration ([Cl^-]_c); (3) whether [Cl^-]_c could change with cell volume change under an isosmotic condition; (4) whether [Cl^-]_c could change under conditions where multiple Cl^- transporters and channels contribute to Cl^- influx and efflux in an isosmotic state; (5) whether the change in [Cl^-]_c could be large enough to act as signals; (6) effects of Cl^- on cytoskeletal tubulin polymerization through inhibition of GTPase activity and tubulin polymerization-dependent biological activity; (7) roles of cytosolic Cl^- in cell proliferation; (8) Cl^--regulatory mechanisms of ciliary motility; (9) roles of Cl^- in sweet/umami taste receptors; (10) Cl^--regulatory mechanisms of with-no-lysine kinase (WNK); (11) roles of Cl^- in regulation of epithelial Na⁺ transport; (12) relationship between roles of Cl^- and H⁺ in body functions.

Thrombospondin-1 (TSP1) contributes to obesity-associated inflammation via activating Toll-like receptor 4 (TLR4). The regulatory role of vitamin D on this pathway has been suggested. This study aimed to investigate the relationship between TSP1/TLR4 pathway and vitamin D in obese and normal weight subjects with different metabolic phenotypes. Thirty obese and thirty normal weight men were selected. Anthropometric parameters and serum TSP1, TLR4, TNF-α, vitamin D, and metabolic profile were determined. Metabolic phenotypes of obese and normal weight subjects were determined. Findings revealed enhanced TSP1/TLR4/TNF-α levels and reduced 25(OH)D levels in obese compared to normal weight subjects and metabolically unhealthy compared to metabolically healthy subjects. TSP1 correlated positively with parameters of unhealthy metabolic profile. TSP1, TLR4 and TNF-α levels significantly negatively correlated with vitamin D levels. In conclusion, vitamin D might exert a regulatory role on TSP1/TLR4 pathway, providing a potential mechanism that links hypovitaminosis D with risk of metabolic dysfunction.

Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and exerkines, such as apelin, adiponectin, leptin, irisin, and chemerin. Exercise and apelin increase thermogenesis and glucose uptake in pregnancy by activating AMPK, PI3K, PGC-1α, AKT1, UCP3, and sarcolipin. Exercise increases apelin levels to reduce preeclampsia symptoms by increasing eNOS, NO, placental growth factor (PlGF), and VEGF and decreasing levels of fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and oxidative stress. A negative relationship has been reported between plasma leptin and VO₂peak/kg and VO₂peak in women with gestational diabetes. In active women, decreases in leptin levels reduce the risk of preeclampsia by ~ 40%. Higher adiponectin levels are associated with greater physical activity and lead to increased insulin sensitivity. Increased adiponectin levels in preeclampsia and exercise counteract inflammatory and atherogenic activities while also having vascular protective effects. Exercise increases irisin levels that correlate negatively with fasting glucose, insulin concentration, and glycosylated hemoglobin levels. Irisin augments mRNA expression levels of UCP1 and cell death-inducing DNA fragmentation factor-like effector A (cidea) to cause browning of adipose tissue, increased thermogenesis, and increased energy consumption. Irisin concentrations in mothers with preeclampsia in the third trimester negatively correlate with systolic and diastolic blood pressure. Expression levels of chemerin, IL-6, and TNF-α are increased in gestational diabetes, and the increases in chemerin in late pregnancy positively correlate with the ratio of sFlt-1 to PlGF as a marker of preeclampsia. The effects of physical exercise on placentokines and exerkines in women at various stages of pregnancy remain poorly understood.

Duchenne muscular dystrophy (DMD) is an inherited disorder with mutations in the dystrophin gene characterized by progressive muscle degeneration and weakness. Therapy such as administration of glucocorticoids, exon skipping of mutant genes and introduction of dystrophin mini-genes have been tried, but there is no radical therapy for DMD. In this study, we used C. elegans carrying mutations in the dys-1 gene as a model of DMD to examine the effects of febuxostat (FBX). We applied FBX to dys-1 mutant animals harboring a marker for muscle nuclei and mitochondria, and found that FBX ameliorates the muscle loss. We next used a severer model dys-1; unc-22 double mutant and found the dys-1 mutation causes a weakened muscle contraction. We applied FBX and other compounds to the double mutant animals and assayed the movement. We found that the administration of FBX in combination of uric acid has the best effects on the DMD model.