日本歯科大学

Sjögren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands. Pilocarpine is used as a symptomatic treatment for xerostomia, and chronic administration has been shown to increase salivary secretion; however, the underlying molecular mechanisms remain unclear. This study examined the effects of pilocarpine administration twice on salivary gland function in non-obese diabetic (NOD) mice, an animal model of SS. Pilocarpine was administered to 16-week-old NOD and wild-type (ICR) mice once a week for 2 weeks, and saliva was collected. Salivary volume, amylase activity, and the expression of aquaporin-5 (AQP5), connective tissue growth factor (Ctgf), and serum-and glucocorticoid-regulated kinase-1 (Sgk1) were examined. The salivary volume in ICR mice was significantly increased following the second administration, but not in NOD mice. No significant differences were observed in the total salivary amylase activity in either ICR or NOD mice. Western blot analysis demonstrated higher AQP5 expression in the membrane fractions and significantly lower expression in the cytosolic fractions of the submandibular glands following pilocarpine administration twice in both ICR and NOD mice, although the total AQP5 protein expression levels did not differ between the two types of mice. Gene expression analysis showed that Ctgf and Sgk1 were significantly upregulated in ICR mice following pilocarpine administration twice, but not in NOD mice. These findings suggest that the mechanism underlying the enhanced gene expression of Ctgf and Sgk1 following pilocarpine administration twice is impaired in NOD mice and that the expression of these genes may be associated with pilocarpine-induced salivary secretion.

Background/Objectives: Understanding changes in dental service utilization is vital for planning effective oral health strategies in aging societies. In this study, we aimed to elucidate nationwide trends in major dental procedures in Japan from fiscal year (FY) 2016 to FY2023, and to assess the age, period, and cohort effects underlying these trends. Methods: Using open data from Japan's National Database of Health Insurance Claims, five procedure types were analyzed: cavity filling, dental calculus removal, tooth extraction, dental crown procedures, and denture procedures. Descriptive analyses were performed to examine the annual and age-specific changes in the number of procedures per 1000 population. Age-period-cohort (APC) analyses were conducted using Poisson regression with spline functions, applying 10-year age groups. Results: From FY2016 to FY2023, restorative and prosthetic procedures, including cavity fillings, crowns, and dentures, demonstrated a steady decline, whereas preventive procedures, such as dental calculus removal increased, particularly among younger age groups. The APC analysis revealed distinct age-, period-, and cohort-related patterns in dental service utilization. Age effects indicated relatively higher rates of prosthetic procedures among older adults, whereas cohort effects suggested generational improvements in oral health. Period effects showed a downward shift beginning in FY2020, temporally aligned with the coronavirus disease pandemic. Conclusions: The combined descriptive and APC analyses indicate evolving patterns in dental service utilization in Japan, characterized by increased preventive care among younger generations and persistent age-related differences in prosthetic service use. These findings provide population-based evidence relevant for planning sustainable oral healthcare systems in aging societies.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide and remains a major unmet medical challenge in aging societies. Although amyloid-β (Aβ) plaques and tau pathology are hallmark features of AD, the limited efficacy of many Aβ- and tau-targeted therapies suggests that AD arises from systemic and cerebral dysfunction. Aging-associated homeostatic failure—including hepatic metabolic, vascular, neuroendocrine, inflammatory, oxidative, and mitochondrial dysfunctions—promotes the accumulation of neurotoxic Aβ and tau species, ultimately driving neurodegeneration and impairing endogenous neuroregeneration. Emerging evidence suggests that regular physical exercise induces metabolic, cardiovascular, and neuroendocrine adaptations, improving hepatic metabolic function, cerebral blood flow, oxygen delivery, mitochondrial activity, waste clearance pathways, and brain health. Exercise-induced musculoskeletal–brain crosstalk further contributes to these benefits through the release of myokines and extracellular vesicles, which facilitate systemic intercellular communication to regulate neurovascular function, neuroplasticity, and neuroregeneration. Collectively, these adaptations reduce chronic inflammation and oxidative stress while enhancing resilience across interconnected peripheral and cerebral systems. Therefore, physical exercise may represent a multifaceted preventive and therapeutic strategy capable of restoring brain–body homeostasis and mitigating AD progression. This comprehensive review discusses aging-associated systemic mechanisms underlying AD pathogenesis and summarizes recent advances in the understanding of exercise-mediated protection against AD progression.

It is difficult to make conventional impressions for maxillofacial prostheses in patients with complicated anatomical structures. In addition, even after fabrication, multiple adjustments are usually needed due to its complex morphology. This article describes a combined conventional and digital workflow for fabricating maxillofacial prostheses. An intraoral scanner was used to obtain three-dimensional (3D) data on the interim prosthesis and oral cavity of the patient with a mandibular defect. The surface data of the interim prosthesis was 3D printed with acrylic to fabricate an occlusal record base. A metal framework was fabricated using a combination of digital methods for design and wax pattern fabrication and conventional methods for metal casting. An acceptable fit and a satisfactory clinical outcome were demonstrated by the digitally fabricated new prosthesis. Intraoral scanning and 3D printing are useful alternatives to conventional impression and casting techniques for fabricating prostheses for maxillofacial patients.

Hereditary sensory and autonomic neuropathies (HSANs) are a group of recessive genetic disorders affecting the sensory and autonomic components of the peripheral nervous system (PNS). Compared with somatosensory dysfunctions, the pathogenesis of visceral dysfunction in HSANs remains understudied. This study investigated the neural circuit mechanisms underlying the arrhythmias observed in conditional Dystonin (Dst) gene-trap mice, an animal model of HSAN type VI (HSAN-VI) in which Cre recombinase inactivates Dst expression in selective neural circuits. Inactivation of the Dst gene in PNS neurons using Advillin-Cre caused the degeneration of sensory and sympathetic ganglionic neurons. This was accompanied by arrhythmia, characterized by increased heart rate variability and irregular pulse frequency, which was prominent under isoflurane anesthesia and occurred in the absence of protein aggregate cardiomyopathy. Furthermore, selective inactivation of the Dst gene in PNS sensory neurons using Vglut2-Cre resulted in similar dysregulation of cardiac rhythm. These findings suggest that arrhythmias caused by Dst mutations arise from the disruption of visceral afferent circuits, and that these neural circuits could be potential therapeutic targets for visceral dysfunction in HSAN-VI.