Effect of reduced repair ability of DNA double strand beaks on cognitive function in neurons

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K12599
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Osaka Prefecture University
• Principal Investigator: Kodak Seiji 大阪府立大学, 理学(系)研究科(研究院), 教授 (00195744)
• Co-Investigator(Renkei-kenkyūsha): SHIRAISHI Kazunori 大阪府立大学, 理学系研究科生物科学専攻, 助教 (40347513)
• Research Collaborator: KASHIWAGI Hiroki 大阪府立大学, 理学系研究科生物科学専攻, 客員研究員 ; SAKAGUCHI Kenta 大阪府立大学, 理学系研究科生物科学専攻, 客員研究員 ; OIE Ayaka 大阪府立大学, 理学系研究科生物科学専攻 ; KANABOSHI Sakura 大阪府立大学, 理学系研究科生物科学専攻
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ニューロン / 神経幹/前駆細胞 / DNA２本鎖切断 / 非相同末端結合 / DNA依存的プロテインキナーゼ / アポトーシス

Outline of Final Research Achievements

We investigated the repair kinetics of X-ray-induced DNA double-strand beaks (DSBs) in mouse neural stem/progenitor cells (NSPCs) and their differentiated neurons by scoring the number of phosphorylated histone H2AX (gamma-H2AX) foci or phosphorylated 53BP1 foci post-irradiation. The DSB repair in neurons differentiated from NSPCs in culture was faster than that in mouse embryonic fibroblasts (MEFs), possibly due to the higher DNA-dependent protein kinase activity, but similar to that in NSPCs. Further, the incidence of p53-dependent apoptosis induced by X-irradiation in neurons was significantly higher than that in NSPCs. This difference in response of X-ray-induced apoptosis between neurons and NSPCs may reflect the difference in the fidelity of non-homologous end joining or the differential sensitivity to DNA damage other than DSBs.

Free Research Field

放射線生物学