Evaluation of biomarkers for major depressive disorder

• Project/Area Number: 16KT0199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Sohya Kazuhiro 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第三部, 室長 (80415207)
• Project Period (FY): 2016-07-19 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: うつ病 / ストレス / 脳機能イメージング / 慢性拘束ストレスモデル / 慢性拘束ストレス / 大うつ病障害 / in vivo2光子脳機能イメージング / 診断バイオマーカー / in vivo 2光子脳機能イメージング法 / 脳神経疾患 / 精神疾患 / 二光子励起蛍光イメージング / トランスレーショナルリサーチ

Outline of Final Research Achievements

Currently, the diagnosis of mental illnesses such as depression is based on the doctor's judgment of subjective symptoms and interviews with patients, and it is extremely difficult to make a diagnosis and prevention with quantitative and objectivity based on biological findings. In order to overcome this situation, it would be necessary to directly monitor the brain and evaluate physiologically the human biomarker for the diagnosis of depression in neurophysiology. In addition, for that purpose, it is necessary to create a model animal for depression and to construct a physiological evaluation method. In this study, we established a method for creating a chronic restraint stress model and an analytical method for assessing stress-induced brain activity.

Academic Significance and Societal Importance of the Research Achievements

大うつ病性障害の動物モデルとして、慢性拘束モデルマウスを確立した。その結果、慢性拘束ストレス負荷によってマウスでは、ストレスホルモンであるコルチコステロンの上昇に加え、抗ストレスホルモンであるテストステロンの上昇が検出されたことから、生体反応はストレス反応だけでなく、ストレスに対する回復反応が同時に起こっていることが示唆された。また、ストレスによって脳活動がどのように変化するかを評価するために、個体差のあるマウスの脳を規格化し定量評価する方法を確立した。この方法によって、異なった個体間でも脳活動を定量評価できるようになった。

Research Products

• [Journal Article] Comparison of physiological and behavioral responses to chronic restraint stress between C57BL/6J and BALB/c mice (2020)
  • Author(s): Tsuchimine Shoko、Matsuno Hitomi、O’Hashi Kazunori、Chiba Shuichi、Yoshimura Aya、Kunugi Hiroshi、Sohya Kazuhiro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 525 Issue: 1 Pages: 33-38
  • DOI: 10.1016/j.bbrc.2020.02.073
  • Peer Reviewed / Open Access
• [Journal Article] Construction of the common cortical space by spontaneous activity and its application in the mouse cortex. (2019)
  • Author(s): O'Hashi K, Sohya K, Matsuno H, Tsuchimine S, Kunugi H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 513 Issue: 4 Pages: 869-874
  • DOI: 10.1016/j.bbrc.2019.04.048
  • Peer Reviewed / Open Access
• [Journal Article] Streamlined sensory motor communication through cortical reciprocal connectivity in a visually guided eye movement task (2018)
  • Author(s): Itokazu Takahide、Hasegawa Masashi、Kimura Rui、Osaki Hironobu、Albrecht Urban-Raphael、Sohya Kazuhiro、Chakrabarti Shubhodeep、Itoh Hideaki、Ito Tetsufumi、Sato Tatsuo K.、Sato Takashi R.
  • Journal Title: Nat Commun Volume: 9 Issue: 1 Pages: 1-14
  • DOI: 10.1038/s41467-017-02501-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Brief Novel Visual Experience Fundamentally Changes Synaptic Plasticity in the Mouse Visual Cortex. (2017)
  • Author(s): Li S, Wang L, Tie X, Sohya K, Lin X, Kirkwood A, Jiang B.
  • Journal Title: Journal of Neuroscience Volume: 37 Issue: 39 Pages: 93539360-93539360
  • DOI: 10.1523/jneurosci.0334-17.2017
  • Peer Reviewed
• [Journal Article] Different effects of rotigotine and ropinirole on cholinergic transmission in the mouse medial prefrontal cortex. (2017)
  • Author(s): Sohya K, O'Hashi K, Toma H, Kunugi H.
  • Journal Title: Psychogeriatrics. Volume: Epub ahead of print Issue: 6 Pages: 502-503
  • DOI: 10.1111/psyg.12254
  • Peer Reviewed
• [Journal Article] Selective Suppression of Local Circuits during Movement Preparation in the Mouse Motor Cortex. (2017)
  • Author(s): Hasegawa M, Majima K, Itokazu T, Maki T, Albrecht UR, Castner N, Izumo M, Sohya K, Sato TK, Kamitani Y, Sato TR.
  • Journal Title: Cell Rep. Volume: 18 Issue: 11 Pages: 26762686-26762686
  • DOI: 10.1016/j.celrep.2017.02.043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Sparse circuit activity during motor preparation in mice (2017)
  • Author(s): 間島 慶、長谷川 征史、糸数 隆秀、眞木 崇州、Albrecht Urban-Raphael、Castner Nora、出雲 麻里子、惣谷 和広、佐藤 達雄、神谷 之康、佐藤 隆
  • Organizer: 日本神経科学学会
• [Presentation] The effect of mouse strain and duration of stress exposure on the depression-like behavioral changes by repeated restraint stress (2017)
  • Author(s): 千葉 秀一 、土嶺 章子、吉村 文、鈴木 仁美、大橋 一徳、惣谷 和広、功刀 浩
  • Organizer: 日本神経科学学会
• [Presentation] ドパミン作動薬（抗パーキンソン薬）による大脳皮質アセチルコリン濃度変化 (2017)
  • Author(s): 功刀浩、惣谷和広、大橋一徳、當麻秀機
  • Organizer: 日本老年精神医学会