Journal of Physiological Sciences最新文献

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.

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.

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.

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.

Fenestration has been reported to enhance Fontan hemodynamics in several cases of Fontan circulation. However, the indication criteria for fenestration remain under discussion. To assess the effectiveness of fenestration in Fontan circulation, we conducted a theoretical analysis using a computational model of the fenestrated Fontan circulation. The cardiac chambers and vascular systems were modeled using the time-varying elastance model and the modified Windkessel model, respectively. When the pulmonary vascular resistance index was 4.01 Wood units m², fenestration significantly reduced central venous pressure from 18.0 to 16.1 mmHg and decreased stressed blood volume from 610 to 555 ml. However, in the models with reduced ventricular end-systolic elastance, increased ventricular stiffness constant, or heightened systemic vascular resistance, the advantages of fenestration were diminished. Thus, fenestration may effectively improve the hemodynamics of Fontan circulation in patients with elevated pulmonary vascular resistance.

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.

Developing strategies to enhance cardiac vagal activity (CVA) is essential for improving mood and managing stress. Although hypoxia inhalation may boost CVA, the optimal acute hypoxic conditions remain unclear. Therefore, we aimed to achieve a comprehensive understanding of the hypoxic conditions required to improve CVA and mood following hypoxia. Twenty-one healthy adults participated in both normobaric hypoxic (NH; FIO₂: 13.5 %) and normoxic (NN; FIO₂: 20.9 %) conditions. We monitored heart rate variability (HRV), percutaneous oxygen saturation (SpO₂), and mood across pre-, hypoxia, and post-sessions and assessed psychophysiological stress using the Baevsky Stress Index (SI). Under hypoxia, SpO₂ decreased to 88.1 %, accompanied by reductions in vagally-mediated HRV, followed by supercompensation post-hypoxia. Additionally, mood declined during hypoxia but rapidly rebounded, correlating with CVA and SI fluctuations. These results indicate that acute low-dose hypoxic gas inhalation at FIO₂: 13.5 % enhances CVA and mood post-hypoxia, offering a practical method for building resilience.

Over the last decade, therapeutic advances in cancer immunotherapy have rapidly progressed, leading to an expansion of clinical trials and the development of novel immune checkpoint inhibitors (ICIs) and combination treatments. While ICIs offer substantial clinical benefits, they are also associated with various side effects, notably concerning endocrine function and potential gonadal damage following the initiation of immunotherapy. Exercise has demonstrated promise in enhancing treatment efficacy, including symptom reduction in cancer patients. Research has also established the benefits of exercise in managing fertility and reproductive health. However, there is limited data on the effectiveness of exercise in mitigating fertility-related side effects specifically in patients undergoing ICIs therapy. Given that a significant number of cancer patients are of reproductive age, it is crucial to address potential sexual side effects and offer fertility preservation options. Ensuring that patients are well-informed and supported in their reproductive health decisions is vital. This review reports the prevalence of immune-related adverse effects linked to fertility in cancer patients undergoing ICIs, explores the potential mechanisms by which ICIs may impact reproductive health, and emphasizes the role of exercise in mitigating these adverse effects.

Brain temperature is strictly regulated by various endogenous mechanisms and significantly contributes to brain function in homeothermic animals, making it an important factor for health. Thermosensitive transient receptor potential (TRP) channels convert temperature information into electrical signals through cation influx. In particular, TRPV4 is involved in the regulation of brain function. TRPV4, constitutively active in neurons through its activation by brain temperature, increases neuronal firing. TRPV4KO mice have electroencephalogram abnormalities, resulting in depression-like and social behavioral abnormalities. This basic function of TRPV4, as a translator of brain temperature information, has been implicated in several diseases, including epilepsy and stress-induced depression. In addition to its neuronal functions, TRPV4 has many key functions in glia and vasculature that depend on brain temperature and contribute to brain activity. In this review, I summarize the importance of TRPV4 activities in relation to brain temperature and focus on how hyperthermia-induced TRPV4 dysfunction exacerbates brain diseases.