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NMDA受容体GluN2Dノックアウトマウスにおける(2R,6R)-ヒドロキシノルケタミンの持続的抗うつ効果の消失
Get PDF新潟大学Niigata University博士（医学）Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has attracted attention for its acute and sustained antidepressant effects in patients with depression. Hydroxynorketamine (HNK), a metabolite of ketamine,exerts antidepressant effects without exerting ketamine’s side effects and has attracted much attention in recent years. However, the detailed pharmacological mechanism of action of HNK remains unclear. We previously showed that the GluN2D NMDA receptor subunit is important for sustained antidepressant-like effects of (R)-ketamine. Therefore, we investigated whether the GluN2D subunit is involved in antidepressant-like effects of (2R,6R)-HNK and (2S,6S)-HNK. Treatment with (2R,6R)-HNK but not (2S,6S)-HNK exerted acute and sustained antidepressant-like effects in the tail-suspension test in wildtype mice. Interestingly, sustained antidepressantlike effects of (2R,6R)-HNK were abolished in GluN2D-knockout mice, whereas acute antidepressant-like effects were maintained in GluN2D-knockout mice. When expression levels of GluN2A and GluN2B subunits were evaluated, a decrease in GluN2B protein expression in the nucleus accumbens was found in stressed wildtype mice but not in stressed GluN2D-knockout mice. These results suggest that the GluN2D subunit and possibly the GluN2B subunit are involved in the sustained antidepressant-like effect of (2R,6R)-HNK.Aimi Yamagishi, Yuiko Ikekubo, Masayoshi Mishina, Kazutaka Ikeda, Soichiro Ide,
Loss of the sustained antidepressant-like effect of (2R,6R)-hydroxynorketamine in NMDA receptor GluN2D subunit knockout mice,
Journal of Pharmacological Sciences,
Volume 154, Issue 3,
2024,
Pages 203-208,
ISSN 1347-8613,
https://doi.org/10.1016/j.jphs.2024.01.008.
(https://www.sciencedirect.com/science/article/pii/S1347861324000082)新大院博(医)第1238
ネフローゼ症候群はマウスにおいて尿細管の細胞増殖関連遺伝子の発現を促進する
Get PDF新潟大学Niigata University博士（医学）Background Massive proteinuria, dyslipidemia, and hypoalbuminemia induced by nephrotic syndrome (NS) secondarily affect tubular cells. We conducted an RNA sequencing (RNA-seq) analysis using a mouse model of focal segmental glomerulosclerosis to clarify the impact of NS on tubular cells.
Methods We used transgenic mice expressing hCD25 in podocytes (Nep25) to induce NS by injecting human CD25-specific immunotoxin (LMB2) at a dose of 0.625 ng/g body weight. Seven days after LMB2 injection, we extracted RNA from the whole kidney and conducted an RNA-seq analysis. Subsequently, we conducted multiple immunostaining and in situ hybridization (ISH) of differentially expressed genes (DEGs) to identify their locations and associated cell types. We also investigated the expression levels of DEGs in an additional mouse model of NS induced by adriamycin.
Results After NS induction, 562 upregulated and 430 downregulated DEGs were identified using RNA-seq. An enrichment analysis revealed the upregulation of cell proliferation-related genes. We observed significant upregulation of Foxm1, a transcription factor linked to cell proliferation. Immunostaining and ISH showed that various tubular cells expressed Mki67 and Foxm1 during NS development. The adriamycin-induced NS model also demonstrated the upregulation of Mki67 and Foxm1 in tubular cells.
Conclusions NS induced the upregulation of cell proliferation-related genes in tubular cells without detectable renal dysfunction. Our findings may contribute to understanding the pathological effects of nephrotic syndrome on tubular cells.Suzuki, Y., Kaseda, R., Nakagawa, Y. et al. Nephrotic syndrome induces the upregulation of cell proliferation-related genes in tubular cells in mice. Clin Exp Nephrol 29, 393–404 (2025). https://doi.org/10.1007/s10157-024-02608-1This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s10157-024-02608-1新大院博(医)第1257
変形性膝関節症における脛骨骨幹部皮質骨幅は、下肢アライメントおよび骨形態と関連している
Get PDF新潟大学博士（医学）Background
The purpose of this study was to clarify (1) the differences in cortical bone thickness (CBT) of the tibial diaphysis between healthy and osteoarthritic knees and (2) the influences of the femorotibial angle (FTA) and inclination of the medial compartment of the proximal tibia (MCT) on tibial CBT.
Methods
The study assessed 60 subjects with varus knee osteoarthritis (OA) (22 males and 38 females; mean age, 74 ± 7 years) and 53 healthy elderly subjects (28 males and 25 females; mean age, 70 ± 6 years). Three-dimensional estimated CBT of the tibial diaphysis was automatically calculated for 2752–11,296 points using high-resolution measurements from CT. The standardized CBT was assessed in 24 regions by combining six heights and four areas. Additionally, the association between the CBT, each FTA, and MCT inclination was investigated.
Results
The OA group showed a thicker CBT in the medial areas than in the lateral areas of the proximal tibia, while the healthy group had a thicker lateral CBT. The medial-to-lateral ratio of the proximal tibia was significantly higher in the OA group than in the healthy group. The proximal-medial CBT correlated with FTA and MCT inclinations in the OA group.
Conclusions
This study demonstrated that varus osteoarthritic knees showed a different trend of proximal-medial CBT with associations in FTA and MCT inclination from healthy knees, possibly due to medial load concentration.Maeda, K., Mochizuki, T., Tanifuji, O. et al. Medial cortical bone thickness of the tibial diaphysis in osteoarthritis is related to lower extremity alignment and tibial morphology. J Orthop Surg Res 19, 355 (2024). https://doi.org/10.1186/s13018-024-04849-y新大院博（医）第1280
歴史的町並みにおける景観保全施策の周辺領域への拡張に関する研究 : 日本の重要伝統的建造物群保存地区と中国の国家歴史文化名城を比較して
Get PDF新潟大学Niigata University博士（工学）新大院博(工)第583