University of the Ryukyus · Faculty of Medicine · 教授

Research keywords膀胱機能低強度衝撃波・排尿障害神経可塑性・糖尿病ラット膀胱活動・骨盤臓器脱GWAS・腸内細菌叢耐糖能予測・前立腺癌ホルモン療法・サルコペニア肥満・膀胱尿管逆流症・尿失禁治療

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• Low-intensity energy shock wave therapy modulates bladder function and anxiety-like behavior in maternal separation rats.2026 · AIMS: To investigate whether low-intensity energy shock wave therapy (LiESWT) applied to the bladder can alleviate maternal separation (MS)-induced lower urinary tract dysfunction and anxiety-like behavior in a rat model. METHODS: Sprague-Dawley rat pups were divided into normal, MS, and MS + LiESWT groups. MS was performed on postnatal days 2-14. At 6 weeks of age, the MS + LiESWT group received shock wave therapy (0.12 mJ/mm2, 2 Hz, 200 shocks per session, nine sessions) in the bladder region. At 9 weeks of age, all groups underwent anxiety-like behavior assessment using the elevated plus maze test, followed by metabolic cage evaluation, cystometry, and histology to assess bladder function and morphology. RESULTS: Compared to normal rats, MS rats exhibited increased bladder weight, shortened intercontraction intervals, and increased anxiety-like behavior. LiESWT treatment normalized bladder weight and improved urinary frequency compared to MS rats, and reduced anxiety-like behavior, as evidenced by recovery of time spent in the open arms of the elevated plus maze. Sex-related differences were observed, with effects being more pronounced in females. This was particularly evident in the voiding frequency during the dark phase and the adrenal gland weight. CONCLUSIONS: LiESWT applied to the bladder improved bladder dysfunction and reduced anxiety-like behavior in MS rats, suggesting potential interactions between bladder function and emotional state that may involve shared neural circuits. The findings indicated the potential therapeutic applications of LiESWT for improving the stress-induced dysfunction affecting the integrated neurobiological pathways that govern both bladder control and behavioral regulation.
• Time-dependent bladder activity changes in streptozotocin-induced female diabetic rats2025 · This study aimed to investigate the long-term physiological and morphological changes in the bladders of diabetic rats. Sixty-nine female Sprague-Dawley rats were divided into a control and six diabetic (3 days and 2, 4, 8, 12, and 24 weeks after induction of type 1 diabetes) groups. Metabolic cages and cystometry were used to evaluate bladder function. Bladder contractility was assessed using an organ bath test, and Masson's trichrome staining was performed. In the metabolic cage study, the urination frequency during the dark period significantly increased in the early stages at 3 days of diabetes (p < 0.05). The voiding interval significantly increased (p < 0.05) at 8-12 weeks of diabetes, while the residual urine volume and voiding efficiency worsened at 24 weeks. In the organ bath study, the dose-response curve of carbachol for median effective concentration did not change; however, the bladder contractile force was enhanced at 8 weeks (p = 0.028). Histological analysis revealed increased fibrosis at 4 weeks of diabetes. Diabetic bladder dysfunction is characterized by storage and voiding bladder activity changes in the early stages that induces urinary frequency and reduced voiding efficiency in the late phase; this turning point occurs at 8 weeks after diabetes.
• Characterization of optogenetically activated inhibitory inputs onto cholinergic motor neurons in the spinal dorsolateral nucleus2025 · Inhibitory control of external urethral sphincter motor neurons (EUS-MNs) in the spinal dorsolateral nucleus (DLN), which corresponds to a portion of Onuf's nucleus in humans, is essential for normal micturition by inducing EUS relaxation during voiding; yet synaptic mechanisms remain poorly characterized. Using neonatal mice P8-P12, we developed a slicing technique-cutting spinal cords at 150° from the coronal plane (30° from the horizontal plane in the agarose block), for maximizing EUS-MNs captured per slice. Using transgenic mice co-expressing channelrhodopsin-2 in inhibitory interneurons (VGAT-ChR2) and GFP in cholinergic neurons (ChAT-GFP), we investigated inhibitory synaptic transmission onto EUS-MNs. Optogenetic activation evoked robust inhibitory postsynaptic potentials (IPSPs), classified as sustained or transient based on temporal profiles. Pharmacology revealed that sustained IPSPs contained both glycinergic and GABAergic components, while GABAA receptors predominantly mediated transient IPSPs. Strychnine (1 μM) selectively blocked glycinergic transmission, while bicuculline (10 μM) eliminated GABAergic components. Insensitivity to glutamatergic antagonists (CNQX and AP5) confirmed purely inhibitory responses. Our findings demonstrate segregation of inhibitory inputs onto EUS-MNs, with glycinergic and GABAergic transmission contributing to sustained and transient inhibition, respectively, establishing the methodological foundation for investigating inhibitory circuit dynamics in pathological conditions such as spinal cord injury with deficient inhibitory control.
• Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study2024 · AIM: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). METHODS: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). RESULTS: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. CONCLUSIONS: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.

• 女性骨盤底弛緩症へのメカノバイオロジーによる戦略的予防システムの構築2025 · 基盤研究(C)
• 中枢ロバストネス変容による加齢膀胱治療抵抗性機序と低出力体外衝撃波の再生効果2025 · 基盤研究(C)
• 低出力体外衝撃波によるメカノバイオロジーの機序解明と加齢による排尿障害治療の確立2024 · 基盤研究(C)
• 幼少期ストレス起因排尿機能障害の末梢―中枢変化と神経可塑性誘導に対する影響の解明2023 · 基盤研究(C)

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