Could neuronal cell senescence be a pathogenetic factor for age-associated neurodegenerative diseases?

• Project/Area Number: 15K08425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kagawa University
• Principal Investigator: Chiba Yoichi 香川大学, 医学部, 講師 (30372113)
• Co-Investigator(Kenkyū-buntansha): 上野 正樹 香川大学, 医学部, 教授 (30322267)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞老化 / 神経変性疾患 / 神経細胞 / 老化促進モデルマウス

Outline of Final Research Achievements

To investigate whether neuronal cell senescence contributes to the pathogenesis of age-associated neurodegenerative diseases, we analyzed the expression of cell senescence markers in cultured primary cortical neurons from E17 embryos of SAMP8 mice, a model for age-associated neurodegeneration. Primary neurons from mouse embryos were successfully maintained in serum-free media for up to 8 weeks. The ratio of senescence-associated β-galactosidase-positive neurons from SAMP8 mice was significantly increased after 28 days in vitro (DIV) when compared to those from control SAMR1 mice. The expression of γ-H2AX, a marker for DNA damage foci, was increased in nuclei of cultured neurons after 28 DIV, although no significant difference between neurons from SAMP8 and SAMR1 mice. Other cell senescence markers, such as heterochromatin-associated mH2A and lipid peroxidation product 4-HNE, did not show significant difference between neurons from SAMP8 and SAMR1 mice.

Research Products

• [Journal Article] SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda’s legacy and future directions. (2017)
  • Author(s): Akiguchi I, Pallàs M, Budka H, Akiyama H, Ueno M, Han J, Yagi H, Nishikawa T, Chiba Y, Sugiyama H, Takahashi R, Unno K, Higuchi K, Hosokawa M.
  • Journal Title: Neuropathology Volume: 印刷中 Issue: 4 Pages: 293-305
  • DOI: 10.1111/neup.12373
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunoreactivity of urate transporters, GLUT9 and URAT1, is located in epithelial cells of the choroid plexus of human brains (2017)
  • Author(s): Uemura Naoya、Murakami Ryuta、Chiba Yoichi、Yanase Ken、Fujihara Ryuji、Mashima Masato、Matsumoto Koichi、Kawauchi Machi、Shirakami Gotaro、Ueno Masaki
  • Journal Title: Neuroscience Letters Volume: 659 Pages: 99-103
  • DOI: 10.1016/j.neulet.2017.09.001
  • Peer Reviewed
• [Journal Article] Glucose transporter 8 immunoreactivity in astrocytic and microglial cells in subependymal areas of human brains (2017)
  • Author(s): Mashima M, Chiba Y, Murakami R, Uemura N, Matsumoto K, Kawauchi M, Kanenishi K, Hata T, Ueno M
  • Journal Title: Neuroscience Letters Volume: 636 Pages: 90-94
  • DOI: 10.1016/j.neulet.2016.11.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunoreactivity of glucose transporter 8 is localized in the epithelial cells of the choroid plexus and in ependymal cells (2016)
  • Author(s): Murakami R, Chiba Y, Tsuboi K, Matsumoto K, Kawauchi M, Fujihara R, Mashima M, Kanenishi K, Yamamoto T, Ueno M
  • Journal Title: Histochemistry and Cell Biology Volume: 146 Issue: 2 Pages: 231-236
  • DOI: 10.1007/s00418-016-1444-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Albumin microvascular leakage in brains with diabetes mellitus (2016)
  • Author(s): Fujihara R, Chiba Y, Nakagawa T, Nishi N, Murakami R, Matsumoto K, Kawauchi M, Yamamoto T, Ueno M
  • Journal Title: Microscopy Research and Technique Volume: 79 Issue: 9 Pages: 833-837
  • DOI: 10.1002/jemt.22708
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions. (2016)
  • Author(s): Ueno M, Chiba Y, Murakami R, Matsumoto K, Kawauchi M, Fujihara R
  • Journal Title: Brain Tumor Pathol Volume: 33 Issue: 2 Pages: 89-96
  • DOI: 10.1007/s10014-016-0255-7
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood-cerebrospinal fluid barrier in human brain. (2015)
  • Author(s): Matsumoto K, Chiba Y, Fujihara R, Kubo H, Sakamoto H, Ueno M
  • Journal Title: Histochem Cell Biol Volume: 144 Issue: 6 Pages: 597-611
  • DOI: 10.1007/s00418-015-1366-7
  • Peer Reviewed
• [Presentation] SAMP8マウスの神経病理 (2017)
  • Author(s): 千葉 陽一
  • Organizer: 第３２回老化促進モデルマウス（SAM）学会