Journal of Physiological Sciences最新文献

The capsaicin receptor TRPV1 was identified as the first heat-activated ion channel in 1997. Since then, numerous studies have been performed on its physiological functions and structure-function relationship, and chemicals targeting TRPV1 have been developed. It has been more than 27 years since the initial cloning of the TRPV1 gene and more than 11 years since the clarification of its structure at the atomic level using cryo-EM. However, we still lack good chemical antagonists of TRPV1 as medicines. TRPV1 is involved in body temperature regulation, but how TRPV1 antagonists cause hyperthermia and how TRPV1 is involved in body temperature regulation are not yet clearly understood. More research is needed in the thermal biology field.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Sleep-wake disorders are an extremely predominant and often disabling aspect of AD. Ox is vital in maintaining the sleep-wake cycle and promoting wakefulness. Dysfunction of Ox signaling has been associated with sleep disorders such as narcolepsy. In AD patients, the increase in cerebrospinal fluid Ox levels is related to parallel sleep deterioration. The relationship between AD and sleep disturbances has gained increasing attention due to their potential bidirectional influence. Disruptions in sleep patterns are commonly observed in AD patients, leading researchers to investigate the possible involvement of Ox in sleep disturbances characteristic of the disease. This review article explores the role of the Ox system in AD, and the intricate relationship between AD and sleep, highlighting the potential mechanisms, impact on disease pathology, and therapeutic interventions to improve sleep quality in affected individuals.

Human skin, as a sophisticated sensory organ, is able to detect subtle changes in ambient temperature. This thermosensory capability is primarily mediated by temperature-sensitive TRP channels expressed in both sensory neurons and keratinocytes. Among these, TRPV3, which responds to warm temperatures and plays a crucial role in various skin functions, is particularly notable. TRPV3 channels not only detect moderate warmth but are also sensitive to chemical ligands that evoke thermal sensations. The activation of TRPV3 by warm temperatures and compounds highlights its importance in the molecular mechanisms underlying skin thermosensation. This review mainly discusses the role of TRPV3, particularly its contribution to skin thermosensation and structural insights into its temperature sensitivity, providing an understanding of how TRPV3 modulates thermal perception at the molecular level.

Reactive oxygen species (ROS) are redox-signaling molecules involved in aging and lifestyle-related diseases. In the brain, in addition to the production of ROS as byproducts of metabolism, expression of ROS synthases has recently been demonstrated, suggesting possible involvement of ROS in various brain functions. This review highlights current knowledge on the relationship between ROS and brain functions, including their contribution to age-related decline in synaptic plasticity and cognitive function. While most studies demonstrate either the positive or negative effects of ROS on synaptic plasticity, the dual effects of ROS at individual synapses have been demonstrated recently in the mouse cerebellum. Furthermore, the cooperative interaction between these two effects determines the direction of synaptic plasticity. It is anticipated that further elucidation of both the positive and negative effects of ROS on brain function will lead to the development of more effective therapeutic strategies with fewer side effects for ROS-related brain dysfunction.

The present study explored the phenotype and behavioral characteristics of mice implanted with the 85As2 human stomach cancer cell lines. Generally, mice are nocturnal; they are active during the dark phase and resting in the light phase. However, mice implanted with 85As2 cells demonstrated diurnal patterns, showing activity in the light phase. The similar light-dark behavioral reversal was noted in mice implanted with other cancer cell lines, such as the HCT116 human colon cancer cell lines. Furthermore, 85As2 implanted mice revealed significant shortening of the free-running period under constant dark conditions. To explore the underlying physiological mechanisms of this circadian rhythm reversal, diurnal variations in the suprachiasmatic nucleus (SCN) were analyzed with observation of c-Fos expression. Interestingly, no significant difference was found in the SCN activity between the control and 85As2-implanted mice, demonstrating rhythm reversal. It is suggested that the lesion causing this rhythm reversal exists downstream of the SCN.

The spectral analysis of heart rate variability (HRV) has long been considered a practical, noninvasive tool to assess autonomic nervous functions that regulate the cardiovascular system. The conventional method, however, has limitations in characterizing transient changes of HRV. We have overcome this problem by adopting the time-frequency analysis method. Using this method, we attempted to clarify differences in the arterial baroreflex (ABR) activity during a transient change in the heart rate between the supine and standing positions in healthy subjects. We found that the ABR gain was significantly greater in the supine position compared to standing, and this gain increase was due to transient increases in 0.15 to 0.20 Hz components of HRV spectral powers caused by enhanced cardiac vagal outflow. Based on these findings, we conclude that the orthostatic stress induced by the postural change from supine to standing markedly reduces the baroreflex gain by suppressing high-frequency cardiac vagal outflow.

There is growing evidence that eicosapentaenoic acid (EPA) uptake has beneficial effects on various cardiovascular diseases. However, electrophysiological actions of EPA remain poorly documented. To investigate the potential antiarrhythmic effects of EPA, mice were fed a high-fat diet (HFD) or an HFD supplemented with EPA for eight weeks. Electrocardiogram (ECG) recordings in combined with esophageal electrical stimulation revealed that HFD-fed mice exhibited bradycardia, reduced P-wave amplitude, and prolonged P-wave duration. Atrial fibrillation (AF) was induced in 100 % of HFD mice, which was only in 50 % of EPA-supplemented mice with significantly shorter durations. HFD-fed mice showed decreased expression of Cav1.2-mRNA, increased expression of Kv1.5-mRNA, elevated expression of inflammatory cytokines (IL-1β, TNF-α, and IL-10), and larger fibrotic area in atrial tissue, which were all reversed by EPA supplementation. These findings suggest that long-term dietary intake of EPA may help maintain normal atrial function and structure, thereby reducing the risk of AF.

FoxO1, a transcription factor, is upregulated in skeletal muscle during atrophy and inactivation of FoxO1 is a potential strategy to prevent muscle loss. This study identified Rebastinib as a potent suppressor of FoxO1 activity among protein kinase inhibitors. To determine whether Rebastinib inhibits atrophy-related ubiquitin ligases gene expression and mitigates atrophy in mouse skeletal muscle-derived cells, we investigated its protective effects of the compound against dexamethasone (DEX)-induced muscle atrophy using C2C12 myotubes. Rebastinib inhibited the DEX-induced upregulation of atrogin-1 and MuRF-1 mRNA, and atrogin-1 protein. Rebastinib also suppressed protein degradation and increased myotube diameter in DEX-treated C2C12 myotubes. Additionally, Rebastinib ameliorated the DEX- and cachexia-induced reduction in contractile force generation. Although the precise mechanisms underlying the action of Rebastinib against muscle atrophy and its efficacy in vivo remains to be elucidated, this compound shows great potential as a therapeutic agent for muscle atrophy.

Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel with high Ca²⁺ permeability. TRPM2 exhibits temperature sensitivity, detecting warm to noxious high temperatures. This temperature sensitivity is regulated by several endogenous factors, including reactive oxygen species, adenosine diphosphate ribose, Ca²⁺ ions, and TRPM2 phosphorylation by protein kinase C, which alter TRPM2 activity at body temperature. Consequently, at core body temperature, TRPM2 regulates the physiological functions of TRPM2-expressing cells and tissues, such as immunocytes, pancreatic β cells, and the brain. In contrast, TRPM2 in sensory neurons detects warm temperatures. The current review summarizes the regulatory mechanisms of TRPM2 and its roles in physiological processes, focusing on temperature-dependent phenomena.

Acupressure on ST36 (Zusanli), located on the lower leg, commonly used to optimize autonomic nerve activity and systemic blood flow in traditional Chinese medicine. However, its efficacy remains controversial. This study hypothesized that a single acupressure on ST36 attenuates sympathetic nerve activity and mitigate skin vasoconstriction in response to cold stimulation. Twelve participants received either 5-min acupressure or sham pressure in the right ST36; subsequently, their left hand was immersed in cold water (10°C) for 10 min. Heart rate (HR), arterial pressure, skin temperature, and blood flow in both fingers were monitored. Autonomic nerve activity was assessed by HR variability. Water immersion decreased skin temperature and blood flow in both fingers with an increase in arterial pressure. However, there were no differences in these values or HR variability between the acupressure and sham trials. Acupressure on ST36 affected neither sympathetic nerve activity nor skin vasoconstrictive response during cold-water immersion.