Journal of Physiological Sciences最新文献

We reviewed fundamental studies on muscular pain, encompassing the characteristics of primary afferent fibers and neurons, spinal and thalamic projections, several muscular pain models, and possible neurochemical mechanisms of muscle pain. Most parts of this review were based on data obtained from animal experiments, and some researches on humans were also introduced. We focused on delayed-onset muscle soreness (DOMS) induced by lengthening contractions (LC), suitable for studying myofascial pain syndromes. The muscular mechanical withdrawal threshold (MMWT) decreased 1-3 days after LC in rats. Changing the speed and range of stretching showed that muscle injury seldom occurred, except in extreme conditions, and that DOMS occurred in parameters without muscle damage. The B2 bradykinin receptor-nerve growth factor (NGF) route and COX-2-glial cell line-derived neurotrophic factor (GDNF) route were involved in the development of DOMS. The interactions between these routes occurred at two levels. A repeated-bout effect was observed in MMWT and NGF upregulation, and this study showed that adaptation possibly occurred before B2 bradykinin receptor activation. We have also briefly discussed the prevention and treatment of DOMS.

L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions.

Experiments measuring evoked potentials require flexible and rapid adjustment of stimulation and recording parameters. In this study, we have developed a recording system and an associated Android application that allow making such adjustments wirelessly. The system consists of 3 units: for stimulation, recording and control. Most of the modules in this system are custom made, although the stimulator and tablet are off-the-shelf products. When installed on the tablet, our Android application allows wireless communication with the control unit from a distance of 5 m. In testing, the recording unit had low internal noise and displayed signals faithfully. Upon receiving commands from the control unit, the stimulation unit produced precisely timed pulse outputs. Using this system, we were able to record evoked field potentials in the dentate gyrus of a rat; responses increased as expected with increasing stimulation pulse amplitude and duration.

Cardiac glycosides, known as inhibitors of Na⁺,K⁺-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na⁺,K⁺-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven genes have been identified as human renal urate transporters. However, it remains unclear whether all renal tubular cells express the same set of urate transporters. Here, we show renal tubular cells are divided into three distinct cell populations for urate handling. Analysis of healthy human kidneys at single-cell resolution revealed that not all tubular cells expressed the same set of urate transporters. Only 32% of tubular cells were related to both reabsorption and secretion, while the remaining tubular cells were related to either reabsorption or secretion at 5% and 63%, respectively. These results provide physiological insight into the molecular function of the transporters and renal urate handling on single-cell units. Our findings suggest that three different cell populations cooperate to regulate urate excretion from the human kidney, and our proposed framework is a step forward in broadening the view from the molecular to the cellular level of transport capacity.

Androgen excess and metabolic abnormality largely contribute to the pathogenesis of polycystic ovarian syndrome (PCOS), which primarily precipitates ovarian dysfunction and infertility in reproductive-age women. Impaired mitochondrial function and epigenetic alteration have been linked to the development of PCOS. However, it is unknown whether acetate would exert a therapeutic effect on ovarian mitochondrial dysfunction in PCOS. Herein, the study hypothesized that acetate reverses ovarian mitochondrial dysfunction in experimental PCOS rat model, possibly through modulation of mitofusin-2 (MFn2). Eight-week-old female Wistar rats were randomized into four groups (n = 5). Induction of PCOS was performed by 1 mg/kg letrozole (p.o.), administered for 21 days. Thereafter, the rats were treated with acetate (200 mg/kg; p.o.) for 6 weeks. The PCOS rats demonstrated androgen excess, multiple ovarian cysts, elevated anti-mullerian hormone and leptin and decreased SHBG, adiponectin and 17-β estradiol with corresponding increase in ovarian transforming growth factor-β1. Additionally, inflammation (tumor growth factor and nuclear factor-kB), elevated caspase-6, decreased hypoxia-inducible factor-1α and elevated histone deacetylase-2 (HDAC2) were observed in the ovaries of PCOS rats, while mitochondrial abnormality with evidence of decreased adenosine triphosphate synthase and MFn2 was observed in rats with PCOS. Treatment with acetate reversed the alterations. The present results collectively suggest that acetate ameliorates ovarian mitochondrial abnormality, a beneficial effect that is accompanied by MFn2 with consequent normalization of reproductive-endocrine profile and ovarian function. Perhaps, the present data provide hope for PCOS individuals that suffer infertility.

The balance of activity between glutamatergic and GABAergic networks is particularly important for oscillatory neural activities in the brain. Here, we investigated the roles of GABA_B receptors in network oscillation in the oral somatosensory cortex (OSC), focusing on NMDA receptors. Neural oscillation at the frequency of 8-10 Hz was elicited in rat brain slices after caffeine application. Oscillations comprised a non-NMDA receptor-dependent initial phase and a later NMDA receptor-dependent oscillatory phase, with the oscillator located in the upper layer of the OSC. Baclofen was applied to investigate the actions of GABA_B receptors. The later NMDA receptor-dependent oscillatory phase completely disappeared, but the initial phase did not. These results suggest that GABA_B receptors mainly act on NMDA receptor, in which metabotropic actions of GABA_B receptors may contribute to the attenuation of NMDA receptor activities. A regulatory system for network oscillation involving GABA_B receptors may be present in the OSC.

We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20-25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET.

There are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood. The Thermal Gradient Ring is a new apparatus that allows mice to freely move around the ring floor and not stay in a corner. The system can analyze various factors (e.g., 'Spent time', 'Travel distance', 'Moving speed', 'Acceleration') associated with temperature-dependent behaviors of TRP-deficient mice. For example, the Ring system clearly discriminated differences in temperature-dependent phenotypes between mice with diabetic peripheral neuropathy and TRPV1^-/- mice, and demonstrated the importance of TRPV3 in temperature detection in skin. Studies using the Thermal Gradient Ring system can increase understanding of the molecular basis of thermal behaviors in mice and in turn help develop strategies to affect responses to different temperature conditions in humans.

The athlete's paradox phenomenon involves the accumulation of intramuscular triglycerides (IMTG) in both insulin-resistant and insulin-sensitive endurance athletes. Nevertheless, a complete understanding of this phenomenon is yet to be achieved. Recent research indicates that lactate, a common byproduct of physical activity, may increase the accumulation of IMTG in skeletal muscle. This is achieved through the activation of G protein-coupled receptor 81 (GPR81) leads to the suppression of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway. The mechanism accountable for the increase in mitochondrial content in skeletal muscle triggered by lactate remains incomprehensible. Based on current research, our objective is to explore the role of the GPR81-inhibited cAMP-PKA pathway in the aggregation of IMTG and the increase in mitochondrial content as a result of prolonged exercise. The GPR81-cAMP-PKA-signaling pathway regulates the buildup of IMTG caused by extended periods of endurance training (ET). This is likely due to a decrease in proteins related to fat breakdown and an increase in proteins responsible for fat production. It is possible that the GPR81-cAMP-PKA pathway does not contribute to the long-term increase in mitochondrial biogenesis and content, which is induced by chronic ET. Additional investigation is required to explore the possible hindrance of the mitochondrial biogenesis and content process during physical activity by the GPR81-cAMP-PKA signal.