Elucidation of the mechanisms by which microglia enhance the functional maturation of blood brain barrier

• Project/Area Number: 17K08330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Sato Kaoru 国立医薬品食品衛生研究所, 薬理部, 室長 (10311391)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ミクログリア / 血液脳関門 / サイトカイン / ケモカイン / 発達 / BBB / 生後発達

Outline of Final Research Achievements

We clarified that the roles of microglia in both of healthy BBB and pathological BBB. Of note, we identified two cytokines are essential to the effects of microglia. These findings will lead to the new therapeutic targets in the CNS diseases associated with BBB breakdown.

Academic Significance and Societal Importance of the Research Achievements

ミクログリアによる正常時の BBB バリア機能調節機構、それに関わるサイトカイン・ケモカインを明らかとすることで、炎症をともなう中枢神経疾患における BBB機能破綻に対するそれらサイトカイン・ケモカインの治療応用性について明らかとした。以上の知見は中枢神経系への薬物送達のための重要な情報となることも期待される。

Research Products

• [Journal Article] Hyaluronan synthesis supports glutamate transporter activity (2019)
  • Author(s): Hayashi MK, Nishioka T, Shimizu H, Takahashi K, Kakegawa W, Mikami T, Hirayama Y, Koizumi S, Yoshida S, Yuzaki M, Tammi M, Sekino Y, Kaibuchi K, Shigemoto-Mogami Y, Yasui M, Sato K.
  • Journal Title: Journal of Neurochemistry Volume: 150 Issue: 3 Pages: 249-263
  • DOI: 10.1111/jnc.14791
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Consideration for future in vitro BBB models — technical development to investigate the drug delivery to the CNS (2018)
  • Author(s): Sato K
  • Journal Title: Folia Pharmacologica Japonica Volume: 152 Issue: 6 Pages: 287-294
  • DOI: 10.1254/fpj.152.287
  • NAID: 130007528447
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 2.Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model (2018)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Sato K
  • Journal Title: Front Cell Neurosci Volume: 12 Pages: 494-494
  • DOI: 10.3389/fncel.2018.00494
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microglia and cellular differentiation — possibility of microglia as drug discovery target (2017)
  • Author(s): Shigemoto-Mogami Y, Sato K.
  • Journal Title: Folia Pharmacologica Japonica Volume: 150 Issue: 6 Pages: 268-274
  • DOI: 10.1254/fpj.150.268
  • NAID: 130006247550
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ミクログリアは血液脳関門機能を発達させる． (2020)
  • Author(s): 最上（重本）由香里，北村（中山）貴美子，干川和枝，Agathe Figarol，松崎典弥，降幡知巳，石田誠一，佐藤 薫
  • Organizer: 第93回薬理学会年会
• [Presentation] サイトカイン・ケモカインを介したミクログリアの中枢神経系発達調節機能． (2020)
  • Author(s): 最上由香里，佐藤 薫
  • Organizer: 日本薬学会第140回年会シンポジウム
• [Presentation] Activated microglia disrupt the blood-brain barrier and induce chemokines and cytokines in a rat in vitro model. (2019)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Sato K
  • Organizer: Glia2019
  • Int'l Joint Research
• [Presentation] Search for the mediators of the communication between microglia and neural stem cells. (2019)
  • Author(s): Shigemoto-Mogami Y, Baba K, Suzuki T, Hoshikawa K, Sato K
  • Organizer: Neuro2019
• [Presentation] What happened to the in vitro blood-brain barrier (BBB) model with activated microglia in the brain side-activated microglia can trigger the BBB disruption and modulate the related chemokines and cytokines via the interactions with astrocytes and blood vessels. (2019)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Sato K
  • Organizer: SfN2019
  • Int'l Joint Research
• [Presentation] 病態を考慮した血液脳関門・生体模倣システムの開発 (2019)
  • Author(s): 最上（重本）由香里、 干川和枝、諫田泰成、佐藤 薫
  • Organizer: 日本薬学会第139年会
• [Presentation] Microglia enhance the functional maturation of blood-brain barrier by regulating the cytokine/chemokine dynamics (2018)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Kanda Y, Sato K
  • Organizer: 第 61 回日本神経化学大会
• [Presentation] The interaction of activated microglia with astrocytes induces changes in cytokine/chemokine concentrations in inflammatory neurovascular unit (2018)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Kanda Y, Sato K
  • Organizer: FENS2018
  • Int'l Joint Research
• [Presentation] Microglia is not the resource but the modulator of the cytokines/chemokines in inflammatory neurovascular unit (2018)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Kanda Y, Sato K
  • Organizer: SfN2018
  • Int'l Joint Research
• [Presentation] Microglia Promote the Functional Maturation of Blood-Brain Barrier by Regulating Cytokine/Chemokine Concentrations (2017)
  • Author(s): Shigemoto-Mogami Y, Hoshikawa K, Sato K
  • Organizer: GLIA2017
  • Int'l Joint Research