Functional analysis of neural stem cells in the circumventricular oragns of adult brain

• Project/Area Number: 16K07027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: MIYATA SEIJI 京都工芸繊維大学, 応用生物学系, 教授 (30243124)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経幹細胞 / 脳 / 脱髄 / 血液脳関門 / 脳室周囲器官 / オリゴデンドロサイト / 修復 / 多発性硬化症 / 脳炎症 / ミクリグリア / 浸透圧 / 炎症

Outline of Final Research Achievements

This research project demonstrated following evidences as for neural stem cells (NSCs) in the circumventricular organs (CVOs) of the adult mouse brains. 1) Existence of astrocyte- and tanycyte-type NSCs in the CVOs. 2) New oligodendrocytes are born from NSCs in the medulla oblongata of EAE-induced demyelinated animals, but remyelination in locally demyelinated area is only recovered by oligodendrocyte progenitor cells. 3) NSCs in the CVOs have dual functions that generate new cells and sense blood-derived molecules or information. 4) Microglia in the CVOs are continuously activated and control proliferation of NSCs.

Academic Significance and Societal Importance of the Research Achievements

成体脳における神経幹細胞は、今まで特定の部位にしか存在していないと考えられてきたが、新たに脳室周囲器官の3部位にも存在することが分かり、幅広い脳部位で新しい細胞の供給が行われていることが分かった。しかし、脳室周囲器官の神経幹細胞の機能については研究報告が極めて少ない。よって、脳室周囲器官の神経幹細胞の機能を明らかにすることは，成体脳における神経幹細胞の意義を解明する上で学術的に意義の高いものである。また、延髄の神経幹細胞は、ダメージを受けた延髄の機能修復にも関与している可能性が示され、臨床への応用なども期待でき社会的意義も高い。

Research Products

• [Journal Article] Oral gavage of capsaicin causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity in the mouse. (2019)
  • Author(s): 2)Inagaki H, Kurganov E, Park Y, Furube E, Miyata S.
  • Journal Title: Physiology & Behavior Volume: 206 Pages: 213-224
  • DOI: 10.1016/j.physbeh.2019.04.015
  • Peer Reviewed
• [Journal Article] VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. (2019)
  • Author(s): Hiratsuka D, Kurganov E, Furube E, Morita M, Miyata S.
  • Journal Title: Journal of Neuroimmunoogy Volume: 332 Pages: 176-186
  • DOI: 10.1016/j.jneuroim.2019.04.016
  • Peer Reviewed
• [Journal Article] Transiently proliferating perivascular microglia harbor M1 type and precede cerebrovascular changes in a chronic hypertension model (2019)
  • Author(s): Koizumi T, Taguchi K, Mizuta I, Toba H, Ohigashi M, Onishi O, Ikoma K, Miyata S, Nakata T, Tanaka M, Foulquier S, Steinbusch HWM, Mizuno T.
  • Journal Title: J Neuroinflammation Volume: 16 Issue: 1 Pages: 79-79
  • DOI: 10.1186/s12974-019-1467-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TLR4 in circumventricular neural stem cells is a negative regulator for thermogenic pathways in the mouse brain. (2018)
  • Author(s): Muneoka S, Murayama S, Nakano Y, Miyata S.
  • Journal Title: Journal of Neuroimmunology Volume: S0165-5728 Pages: 30497-6
  • DOI: 10.1016/j.jneuroim.2018.04.017
  • Peer Reviewed
• [Journal Article] Remyelination in the medulla oblongata of adult mouse brain during experimental autoimmune encephalomyelitis. (2018)
  • Author(s): Hiratsuka D, Furube E, Taguchi K, Tanaka M, Morita M, Miyata S.
  • Journal Title: Journal of Neuroimmunology Volume: 319 Issue: 1 Pages: 41-54
  • DOI: 10.1038/s41598-018-20643-3
  • Peer Reviewed / Open Access
• [Journal Article] Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation. (2018)
  • Author(s): Furube E, Kawai S, Inagaki H, Takagi S, Miyata S.
  • Journal Title: Scientific Reports Volume: 8
  • Peer Reviewed
• [Journal Article] Microglia are continuously activated in the circumventricular organs of mouse brain. (2017)
  • Author(s): Takagi S, Furube E, Nakano Y, Morita M, Miyata S.
  • Journal Title: Journal of Neuroimmunology Volume: S0165-5728 Pages: 30384-3
  • DOI: 10.1016/j.jneuroim.2017.10.008
  • Peer Reviewed
• [Journal Article] Advances in Understanding of Structural Reorganization in the Hypothalamic Neurosecretory System (2017)
  • Author(s): Miyata S
  • Journal Title: Frontier in Endocrinology (Lausanne) Volume: 8
  • DOI: 10.3389/fendo.2017.00275
  • Peer Reviewed
• [Journal Article] Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis during an Osmotic Stimulation. (2017)
  • Author(s): Nishikawa K, Furube E, Morita-Takemura S, Horii-Hayashi N, Nishi M, Miyata S.
  • Journal Title: J Neuroendocrinol Volume: 29 Issue: 2
  • DOI: 10.1111/jne.12456
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation. (2016)
  • Author(s): Yoshida A, Furube E, Mannari T, Takayama Y, Kittaka H, Tominaga M, Miyata S
  • Journal Title: Sci Rep. Volume: 18 Issue: 1 Pages: 26088-26088
  • DOI: 10.1038/srep26088
  • Peer Reviewed / Open Access
• [Journal Article] Heterogenous vascular permeability and alternative diffusion barrier in the sensory circumventricular organs of adult mouse brain (2015)
  • Author(s): Morita, S, Furube, E, Mannari, T, Okuda, H, Tatsumi, K, Wanaka, A, Miyata, S
  • Journal Title: Cell and Tissue Research Volume: 0 Issue: 2 Pages: 0-0
  • DOI: 10.1007/s00441-015-2207-7
  • Peer Reviewed / Open Access
• [Journal Article] Protein phosphorylation in encystment-induced Colpoda cucullus: localization and identification of phosphoproteins. (2012)
  • Author(s): Sogame, Y.
  • Journal Title: FEMS Microbiol. Lett. Volume: 331 Issue: 2 Pages: 128-135
  • DOI: 10.1111/j.1574-6968.2012.02560.x
  • Peer Reviewed
• [Presentation] 延髄最後野と中心管の神経幹細胞から三叉神経主感覚核と脊髄路核への新生ニューロン供給 (2018)
  • Author(s): 9)安本拓樹、古部瑛莉子、平塚大士、森田光洋、宮田清司
  • Organizer: 第41回日本神経科学会（神戸）
• [Presentation] マウス視床下部におけるTRPM8発現ニューロンの局在と機能 (2018)
  • Author(s): 10)岡本果穂、高山靖規、富永真琴、宮田清司
  • Organizer: 第41回日本神経科学会（神戸）
• [Presentation] マウス脈絡叢における血管内皮細胞の増殖と水頭症における変化 (2018)
  • Author(s): 12)浅見歩、宮田清司
  • Organizer: 第41回日本神経科学会（神戸）
• [Presentation] 脳室周囲領域は神経幹細胞ニッチェとして広く機能する (2018)
  • Author(s): 13)古部映莉子、森田光洋、宮田清司
  • Organizer: 第41回日本神経科学会（神戸）
• [Presentation] Generation of new oligodendrocytes in the medulla oblongata of mice by EAE-induced demyelination (2017)
  • Author(s): Hiratsuka D, Furube E, Morita M, Miyata S
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Diversity of microglia in the brain: LPS-induced proliferation and expression of M1 and M2 protein (2017)
  • Author(s): Takagi S, Furube E, Miyata S
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Localization of neural stem cells and stroke-induced generation of new neurons and glia in the medulla oblongata (2017)
  • Author(s): Furube E, Hiratsuka D, Taguchi K, Tanaka M, Morita M, Miyata S
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
• [Presentation] strocytes and ependymal cells of the circumventricular organs acts as thermostat during lipopolysaccharide-indued hyperthermia (2017)
  • Author(s): Inagaki H, Muneoka S, Yoshida A, Miyata S
  • Organizer: 第４０回日本神経科学会大会
• [Presentation] Multifunctional neural stem cells in the sensory circumventricular organs of adult mouse (2016)
  • Author(s): 古部瑛莉子、河合晋太郎、稲垣春奈、宮田清司
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Expression of connexin43 at astrocytes in the nucleus of the solitary tract (2016)
  • Author(s): 石崎陽平、宮田清司
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Robust microglial increase in certain brain stem regions after a single LPS stimulation (2016)
  • Author(s): 河合晋太郎、古部瑛莉子、宮田清司
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Activation of TLR4-NF-kB signaling in the circumventricular organs by LPS stimulation (2016)
  • Author(s): 宗岡詩織、宮田清司
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] LPS単発投与によるミクログリア密度の一過性増加：脳部位によるheterogeneity (2016)
  • Author(s): 古部瑛莉子、河合晋太郎、稲垣春奈、宮田清司
  • Organizer: 日本解剖学会第92回近畿支部学術集会
  • Place of Presentation: 大阪狭山市
• [Presentation] 神経分泌状態に依存した下垂体後葉血管系の構造的変化血管周細胞ペリサイトの果 たす役割 (2016)
  • Author(s): 西川和範、 古部瑛莉子、 森田晶子、 堀井謹子、 西真弓、 宮田清司
  • Organizer: 日本解剖学会第92回近畿支部学術集会
  • Place of Presentation: 大阪狭山市
• [Presentation] 脳のTRPV1はSTAT3シグナリングと体温調節経路の活性化に重要である (2016)
  • Author(s): 吉田亜矢加、古部瑛莉子、萬成哲也、稲垣春那、富永真琴、宮田清司
  • Organizer: 日本解剖学会第92回近畿支部学術集会
  • Place of Presentation: 大阪狭山市
• [Presentation] Role of neural stem cells in the sensory circumventricular organs of adult mouse (2016)
  • Author(s): 古部瑛莉子、森田光博、宮田清司
  • Organizer: 第46回北米神経科学会議
  • Place of Presentation: サンディエゴ
  • Int'l Joint Research
• [Remarks] 生体機能学ホームページ
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• [Remarks]
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