Published papers

近年の少子高齢化に伴い、高齢者の健康寿命延伸は重要な課題の1つである。脳の健康状態を維持することは、高齢者の健康寿命延伸につながる。そこで、本研究では、住宅内の温熱環境と脳機能の関係について、2016年度から2022年度まで継続して実測調査を実施している。その結果、居間の床近傍室温が高いと、5年経過後の脳神経線維の得点低下を抑制できる可能性が示された。

執務中の身体活動は長期的な健康だけでなく、交感神経の活性化や脳血流の増加による知的生産性の向上が期待されている。既往研究では、休憩中の歩行が交感神経の活性化を介して知的生産性を向上させる可能性が示されている。しかし、執務者を対象に、活動量の個人間の違いや、日ごとの違いに着目した研究は少ないと言える。そこで、本研究で執務者を対象にアンケート調査を実施し、活動量が執務者に及ぼす影響について分析した。

Cynomolgus monkeys, like humans, are continuous breeders and while the female sexual cycle has been extensively studied, little is known about male sexual cycles, such as periodic changes in the testicle size. Although testosterone, the primary male hormone secreted by the testicles, has been demonstrated to increase pain thresholds in humans and animals, whether testicle size affects pain thresholds is unknown. In the present study, we measured the testicle size in 7 matured male cynomolgus monkeys (6-8 years old) once a week for 23 weeks and observed that there were periodic changes in testicle size, with an average interval between peak points of 36.5 days. We also examined pain thresholds in these animals by measuring paw withdrawal temperatures (PWTs) in the dorsal hind paws once a week for 22 weeks. Similar to the testicles, PWTs underwent periodic changes with an average interval between peak points of 27.6 days. Although their cycles were not synchronized, the mean values of testicle size and PWTs showed a significant correlation (P = 0.019). These results demonstrate the presence of male sexual cycle and indicate the relationship between testicle size and pain thresholds in cynomolgus monkeys, providing new insights into research not only in primates, but also in other continuous breeders, including humans.

循環器疾患やCOVID-19重症化に繋がるとされる高血圧の予防が急務となっている。寒冷環境に曝されると血圧が上昇し、末梢の血行も悪化する。また、COVID-19感染拡大防止のため在宅勤務を行う人が増加しており、住宅における知的生産性の向上が求められている。そこで、本研究では断熱性能の異なるモデルルームで被験者実験を行い、住宅の断熱性能による温熱環境の違いが生理学的反応・在宅勤務を模擬した作業成績に及ぼす影響の検討を行う。

To promote UAM adoption in society, it is necessary to accurately assess the impact of UAM flights on people’s unconscious sensibilities. However, flying UAMs to measure these unconscious sensibilities incurs high costs. Therefore, instead of flying actual UAMs, it is conceivable to measure the unconscious sensibilities when people view CG of flying UAMs. The issue here is the potential discrepancy in the sensibilities people experience when exposed to real versus CG UAM flights. Previous studies attempted to evaluate this sensitivity discrepancy by using a small drone instead of UAMs. However, they could perform little statistical analysis due to the small sample size. This study gathered a larger number of participants than previous research and measured the sensitivity responses elicited by the flight of real and CG drones. Statistical hypothesis testing was then performed, and discrepancies were detected in two sensitivity indices. Furthermore, for the other sensitivity indices where no discrepancy was detected, the sample size required to detect a discrepancy was estimated.

Purpose : The photostimulation of the external environment serves as a visual signal, as well as a non-visual signal through the protein opsin. In mammals, the non-visual photoreceptor opsin5 (also known as OPN5 or neuropsin) is expressed in the retinal ganglion cells RGCs) and hypothalamus. Violet light with a wavelength of 360-400 nm activates OPN5 and regulates the circadian cycle, thermogenesis, and myopia. However, the function of violet light and OPN5 in brain function is unknown. Methods : We exposed aged mice to violet light and observed the effects on memory through contextual fear conditioning and the Barnes maze. In addition, we observed he effects on mood through a social defeat stress (SDS) model and a subsequent social interaction test. We analyzed neural activity and oligodendrogenesis in the SDS model through immunostaining for c-fos and MBP, and examined the projection pathway from OPN5-positive retinal ganglion cells to the brain using WGA and Opn5cre; Ai14 mice. Results : Our results showed that violet light, as an external stimulus, regulates memory and mood function in the brain. Violet light improves memory function in aged mice and simultaneously increases the expression of oligodendrocyte-related genes such as MBP and MAG in the hippocampus. In addition, violet light improves depressive-like behaviors in the social defeat stress model in an OPN5-dependent manner and increases neural activity and oligodendrogenesis in the prefrontal cortex and nucleus accumbens. The neural network analysis using WGA and Opn5cre; Ai14 mice indicates that the signal received by OPN5-positive retinal ganglion cells is transmitted to the habenula brain region. Conclusions : Our findings revealed a novel function for violet light in regulating cognitive function and mood behavior. The well-conserved OPN5 may be a non-visual photoreceptor for sensing the light environment and maintaining brain function throughout the lifespan. Although OPN5-RGCs project to the MHb, the central mechanism sensing VL needs to be further investigated. The role of violet light via OPN5 in underpinning myelination and oligodendrocyte function in influencing cognition and mood behavior opens an interesting new avenue for research and the development of novel therapeutic treatments for neurodegeneration and neuropsychiatry disorders.

Light is perceived through the retina, the light-sensing tissue layer of the eye, and can directly influence the brain. Light exposure triggers various biological responses that improve sleep quality and stabilize mood. Recently, violet light, exhibiting a unique wavelength of 360–400 nm, has garnered significant attention due to its perception through a specific receptor, marking a novel research area. Herein, we used “violet light glasses” that directly emit violet light into the human eye and investigated their effects on healthy humans in real-life settings. This study demonstrated that two hours of violet light exposure in the morning enhanced sleep quality in approximately 20% of the healthy participants and was also associated with improved blood glucose levels. Although this was a pilot study due to its small sample size, our findings indicate that violet light could potentially promote health benefits in humans.

Neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease share a common pathological hallmark: the accumulation of misfolded proteins, particularly involving intrinsically disordered proteins (IDPs) like TDP-43, FUS, Tau, α-synuclein, and Huntingtin. These proteins undergo pathological aggregation, forming toxic inclusions that disrupt cellular function. The dysregulation of proteostasis mechanisms, including the ubiquitin-proteasome system (UPS), ubiquitin-independent proteasome system (UIPS), autophagy, and molecular chaperones, exacerbates these proteinopathies by failing to clear misfolded proteins effectively. Emerging therapeutic strategies aim to restore proteostasis through proteasome activators, autophagy enhancers, and chaperone-based interventions to prevent the toxic accumulation of IDPs. Additionally, understanding liquid-liquid phase separation (LLPS) and its role in stress granule dynamics offers novel insights into how aberrant phase transitions contribute to neurodegeneration. By targeting the molecular pathways involved in IDP aggregation and proteostasis regulation, and better understanding the specificity of each component, research in this area will pave the way for innovative therapeutic approaches to combat these neurodegenerative diseases. This review discusses the molecular mechanisms underpinning IDP pathology, highlights recent advancements in drug discovery, and explores the potential of targeting proteostasis machinery to develop effective therapies.