Research Project
Grant-in-Aid for Scientific Research (C)
We have developed a new animal model of depression by modifying the water maze learning task in mice. When the difficulty of the task is increased by downsizing of the platform and removing external cues, some of the mice gradually abandon adaptive learning and become immobile; this response indicates a depression-like states. In this research, DNA microarray analysis of hippocampus was performed to investigate the genes contributing to depression-like phenotypes of the helpless mice. The analysis followed by validation using real-time PCR revealed significant alteration in the expression of several genes, including downregulation of Ttr (transthyretin). Thus, it is possible that the decrease in Ttr expression in the hippocampus may be involved in the induction of depressant-like states in mice.
本研究で扱ったうつ動物モデルは、遺伝的相同性が極めて高い近交系マウスを被験体としながら、うつ的状態に陥る個体と健常性を維持する個体を並行して得ることができる実験系である。今回、うつ的状態に陥った個体の海馬において発現低下が認められたTtr(トランスサイレチン)は、エピジェネティックなメカニズムの制御を受けて抗うつ効果の発現に関わっていると推測される遺伝子である。つまり、マウスのうつ的状態の誘発には、Ttr等の遺伝子のエピジェネティックなメカニズムを介した変化が関わっている可能性が示唆された。
All 2019 2018 2017 2016
All Journal Article (6 results) (of which Peer Reviewed: 6 results, Open Access: 2 results, Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)
Brain Research
Volume: 1711 Pages: 58-67
10.1016/j.brainres.2018.12.042
Volume: 1712 Pages: 139-150
10.1016/j.brainres.2019.01.037
Neuroscience
Volume: 408 Pages: 147-160
10.1016/j.neuroscience.2019.04.003
Molecular Medicine Reports
Volume: 16 Issue: 1 Pages: 301-309
10.3892/mmr.2017.6577
行動科学
Volume: 55 Pages: 1-11
40021180529
Cell Reports
Volume: 17 Issue: 8 Pages: 2004-2014
10.1016/j.celrep.2016.10.073