The functional role of perivascular scavenger cells in the maintenance of brain homeostasis

• Project/Area Number: 17K01983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Matsuno Hitomi 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, リサーチフェロー (40415302)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: マクロファージ / ミクログリア / 血管脳関門 / うつ病 / ストレス / 脳内炎症 / 神経―血管―グリアユニット / 脳血管関門 / 神経科学

Outline of Final Research Achievements

In the central nervous system, resident macrophages play important roles for immune responses against inflammation, and brain repair mechanism. We performed in vivo imaging of cerebro-vascular structures, and identified brain perivascular macrophages (PVMs). We found that dye-labeled PVM is difference cell type from microglia, and PVMs were apposed to blood vessel walls in both brain surface and deeper brain layers. They actively uptook fluorescence dyes, and persistently accumulated dyes in the granular structures of the cytoplasm. To characterize the functional roles of PVMs in the pathological condition, we investigated the dynamics of PVM in the stress-induced mouse depression model. Chronic restraint stress induced abnormal increase of vascular permeability as well as decline in the number of CD163-positive PVM. These results suggest that PVM may play principle functions for the clearance of waste materials in the perivascular spaces to maintain homeostasis balance.

Academic Significance and Societal Importance of the Research Achievements

本研究では脳常在マクロファージの一つであるPVMについて、うつ病モデルマウスにおける動態変化を解析した。その結果、慢性ストレスはPVMの機能低下を引き起こすことが示唆された。本研究で得られた結果はうつ病だけでなく血管障害を伴う脳疾患の新規治療法やバイオマーカー開発につながることが期待される。

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
• [Presentation] Comparisons between C57BL6/J and BALB/c mice in behavioral test and physiological change after chronic restraint stress. (2019)
  • Author(s): Tsuchimine S, Matsuno H, Ohashi K, Chiba S, Yoshimura A, Nakajima S, Ishiwata S, Ogawa S, Sohya K, Kunugi H
  • Organizer: 第42回日本神経科学大会 (Neuro2019).
• [Presentation] A role of brain macrophages to constitute Blood-brain barrier ー 血液脳関門におけるマクロファージの役割ー (2018)
  • Author(s): Kazunori O’Hashi, Hitomi Matsuno, Shoko Tsuchimine, Shuich Chiba, Kazuhiro Sohya and Hiroshi Kunugi
  • Organizer: 第41回日本神経科学大会