Mechanism for microglia involvement of the brain higher function

• Project/Area Number: 26460325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Akema Tatsuo 聖マリアンナ医科大学, 医学部, 名誉教授 (60128585)
• Co-Investigator(Kenkyū-buntansha): 藤原 清悦 聖マリアンナ医科大学, 医学部, 講師 (10440322) ; 黒坂 光寿 聖マリアンナ医科大学, 医学部, 助教 (40553970) ; 舩橋 利也 聖マリアンナ医科大学, 医学部, 教授 (70229102)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ミクログリア / 海馬 / 学習 / シナプス / 行動解析 / 行動 / 生化学 / AMPA受容体 / 消去 / 可塑性 / 再固定 / グルタミン酸受容体 / AMPA受容体サブユニット / ミノサイクリン / 受動的回避学習 / Wistar雄性ラット / GluR1サブユニット

Outline of Final Research Achievements

Microglia specific inhibitor, minocycline was administered before and after passive avoidance task in male rats. As the results, minocycline injection shortened the time enter the dark box. This means that the blocking of microglia activation attenuated the establishment of bad memory formation. We also analyzed AMPA receptor subunit expression. We revealed that phosphorylation status of 845 serine thus PKA might be changed. Next, we examined this task in mice. In mice, minocycline injection might attenuate the reconsolidation process hereby long-term bad memory formation was attenuated.

Research Products

• [Journal Article] Early Growth Response 3 (Egr3) Contributes a Maintenance of C2C12 Myoblast Proliferation (2017)
  • Author(s): Kurosaka M, Ogura Y, Funabashi T, Akema T
  • Journal Title: J Cell Physiol Volume: 232 Issue: 5 Pages: 1114-1122
  • DOI: 10.1002/jcp.25574
  • Peer Reviewed
• [Journal Article] Involvement of Transient Receptor Potential Cation Channel Vanilloid 1 (TRPV1) in Myoblast Fusion (2016)
  • Author(s): Kurosaka M, Ogura Y, Funabashi T, Akema T
  • Journal Title: J Cell Physiol Volume: 231 Issue: 10 Pages: 2275-85
  • DOI: 10.1002/jcp.25345
  • Peer Reviewed
• [Journal Article] Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats (2015)
  • Author(s): Fukushima A, Ogura Y, Furuta M, Kakehashi C, Funabashi T, Akema T
  • Journal Title: Brain Research Volume: 1622 Pages: 36-42
  • DOI: 10.1016/j.brainres.2015.06.016
  • Peer Reviewed
• [Journal Article] Regeneration of Injured Tibialis Anterior Muscle in Mice in Response to Microcurrent Electrical Neuromuscular Stimulation with or without Icing (2015)
  • Author(s): Atsuhiro Yoshida, Hiroto Fujiya, Katsumasa Goto, Mitsutoshi Kurosaka, Yuji Ogura, Kanaka Yatabe, Hirotaka Yoshioka, Koh Terauchi, Toshiya Funabashi, Tatsuo Akema, Hisateru Niki, Haruki Musha
  • Journal Title: Journal of St. Marianna University Volume: (2):159-169 Pages: 159-169
  • NAID: 130005114670
  • Peer Reviewed
• [Journal Article] Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus. (2015)
  • Author(s): Fukushima A, Hagiwara H, Fujioka H, Kimura F, Akema T, Funabashi T.
  • Journal Title: Front Neurosci Volume: 9 Pages: 1-8
  • DOI: 10.3389/fnins.2015.00088
  • Peer Reviewed / Open Access
• [Journal Article] Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis. (2015)
  • Author(s): Furuta M, Ninomiya-Baba M, Chiba S, Funabashi T, Akema T, Kunugi H.
  • Journal Title: Horm Behav Volume: 70 Pages: 30-37
  • DOI: 10.1016/j.yhbeh.2015.01.010
  • Peer Reviewed
• [Journal Article] Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis (2015)
  • Author(s): Furuta M, Ninomiya-Baba M, Chiba S, Funabashi T, Akema T, Kunugi H
  • Journal Title: Horm Behav. Volume: 70 Pages: 30-37
  • Peer Reviewed
• [Journal Article] Expression of phosphorylated cyclic AMP response element-binding protein in melanin-concentrating hormone neurons and orexin neurons in male and female rats during ad-libitum feeding (2014)
  • Author(s): Fukushima A, Hagiwara H, Yoshioka N, Kimura F, Akema T, Funabashi T
  • Journal Title: Neuroreport. Volume: 25 Issue: 10 Pages: 766-770
  • DOI: 10.1097/wnr.0000000000000172
  • Peer Reviewed
• [Presentation] 雌ラットにおけるプロスタグランジンE2のGnRHニューロン微小EPSCへの影響 (2017)
  • Author(s): 藤岡仁美、明間立雄、舩橋利也
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松コングレスセンター（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] 恐怖条件付け後の海馬高周波と関連した海馬―扁桃体間のγ活動 (2017)
  • Author(s): 藤原清悦、久保田隆、舩橋利也、明間立雄
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松コングレスセンター（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] Gamma band oscillation between hippocampus and amygdala associated with hippocampal high frequen-cy oscillation and fear memory (2016)
  • Author(s): 藤原清悦、久保田隆、舩橋利也、明間立雄
  • Organizer: ライフエンジニアリングシンポジウム2016
  • Place of Presentation: 大阪国際交流センター（大阪府大阪市）
  • Year and Date: 2016-11-03
• [Presentation] 分界条床核におけるCRHニューロンのシナプス入力の性差 (2016)
  • Author(s): 萩原裕子、崎村建司、井樋慶一、明間立雄、舩橋利也
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-07-20
• [Presentation] リポポリサッカライドによるLHサージ状分泌抑制に関与する終板脈絡器官のIL-1β産生細胞の特徴 (2016)
  • Author(s): 藤岡仁美、福島篤、舩橋利也、明間立雄
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-07-20
• [Presentation] 恐怖条件付け後における海馬高周波出現時の扁桃体θおよびγ活動 (2016)
  • Author(s): 藤原清悦、久保田、舩橋利也、明間立雄
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-07-20
• [Presentation] Phosphorylation of signal transduction and activator of transcription 5 (STAT5) in the mouse liver involves high-fat diet (HFD)-induced obesity and glucose intolerance via platelet-derived growth factor receptor alpha (PDGFRα) (2016)
  • Author(s): Atsushi Fukushima, Hiroko Hagiwara, Tatsuo Akema, Toshiya Funbashi
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-24
• [Presentation] Minocycline did not affect the suppression by lipopolysaccharide of pulsatile luteinizing hormone secretion in ovariectomized rats (2016)
  • Author(s): Hitomi Fujioka, Atsushi Fukushima, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-23
• [Presentation] Effects of postnatal nicotine exposure and maternal-like behavior on maternal behavior and spatial learning in adulthood of female rats (2016)
  • Author(s): Miyako Furuta, Atsushi Fukushima, Tatsuo Akema, Toshiya Funabashi
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-23
• [Presentation] STAT6シグナルは筋サテライト細胞の分化と融合を制御する (2016)
  • Author(s): 黒坂光寿、小倉裕司、舩橋利也、明間立雄
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
• [Presentation] Early growth response 3 (Egr3)は筋芽細胞の増殖に関与する (2016)
  • Author(s): 小倉 裕司、黒坂 光寿、舩橋 利也、明間 立雄
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
• [Presentation] 絶食によりマウス視床下部のオリゴデンドロサイト前駆細胞のPDGFRaを介したシグナルは刺激されるが、高脂肪食によりこの調節系が障害される (2015)
  • Author(s): 福島 篤, 萩原 裕子, 舩橋 利也, 明間 立雄
  • Organizer: 第42回日本神経内分泌学会
  • Place of Presentation: 仙台市戦災復興記念館（宮城県仙台市）
  • Year and Date: 2015-09-19
• [Presentation] エストロジェンによる摂食調節は視床下部のオリゴデンドロサイト前駆細胞のPDGFRαを介する (2015)
  • Author(s): 萩原裕子, 福島篤, 舩橋利也, 明間立雄
  • Organizer: 第42回日本神経内分泌学会
  • Place of Presentation: 仙台市戦災復興記念館（宮城県仙台市）
  • Year and Date: 2015-09-19
• [Presentation] プロスタグランジンE2のGnRHニューロンminiature EPSCへの影響 (2015)
  • Author(s): 藤岡仁美, 舩橋利也, 明間立雄
  • Organizer: 第42回日本神経内分泌学会
  • Place of Presentation: 仙台市戦災復興記念館（宮城県仙台市）
  • Year and Date: 2015-09-18
• [Presentation] 妊娠、出産、子育て経験後の学習機能の向上とAMPA受容体サブユニットの構成の変化 (2015)
  • Author(s): 古田 都、福島 篤、舩橋 利也、明間 立雄
  • Organizer: 第42回日本神経内分泌学会
  • Place of Presentation: 仙台市戦災復興記念館（宮城県仙台市）
  • Year and Date: 2015-09-18
• [Presentation] The effect of maternal experiences on hippocampal neural plasticity and spatial learning (2015)
  • Author(s): Miyako Furuta, Atsushi Fukushima, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 国際会議場神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2015-07-29
• [Presentation] Synchronous theta band oscillation between hippocampus and amygdala associated with hippocampal high frequency oscillation during rest time after aversive stimuli correlate with freezing behavior (2015)
  • Author(s): Sei-etsu Fujiwara , Takafumi Kubota, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 国際会議場神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2015-07-29
• [Presentation] High-fat diet feeding impaired platelet-derived growth factor receptor alpha (PDGFRα) up-regulation induced by fasting in NG2-positive oligodendrocyte precursor cells of the hypothalamus in mice (2015)
  • Author(s): Atsushiu Fukushima, Hiroko Hagiwara, Mayuko Moya, Toshiya Funabashi, Tatsuo Akema
  • Organizer: the 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: 国際会議場, 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Estrogen increases the expression of platelet-derived growth factor receptor alpha (PDGFRα) in NG2-positive oligodendrocyte precursor cells of the hypothalamus in rats (2015)
  • Author(s): Hiroko Hagiwara, Atsushiu Fukushima, Toshiya Funabashi, Tatsuo Akema
  • Organizer: the 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: 国際会議場, 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Relation between hippocampal sharp wave ripple events and prefrontal theta activities during delayed reinforcement task (2015)
  • Author(s): Sei-etsu Fujiwara, Yoshinori Izaki, Toshiya Funabashi, Tatsuo Akema
  • Organizer: the 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: 国際会議場, 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] "Synchronized high frequency oscillation and the theta oscillation between the hippocampus and the amygdala after fear conditioning correlates freezing behavior" (2015)
  • Author(s): Takafumi Kubota, Sei-etsu Fujiwara, Toshiya Funabashi, Akema Tatsuo
  • Organizer: the 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: 国際会議場, 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 絶食時に視床下部のミクログリアがPDGFR-aを介して摂食調節に関与する仮説 (2014)
  • Author(s): 福島篤、萩原裕子、藤岡仁美、舩橋利也、明間立雄
  • Organizer: 第41回日本神経内分泌学会学術集会
  • Place of Presentation: 都道府県会館, 東京
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 急性ストレスによるLH分泌抑制へのミクログリアの関与 (2014)
  • Author(s): 藤岡仁美, 福島篤, 舩橋利也, 明間立雄
  • Organizer: 第41回日本神経内分泌学会学術集会
  • Place of Presentation: 都道府県会館, 東京
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 妊娠、出産、子育て後の学習機能の向上ーAMPA受容体サブユニットに着目して (2014)
  • Author(s): 古田 都、福島 篤、舩橋利也、明間立雄
  • Organizer: 第41回日本神経内分泌学会学術集会
  • Place of Presentation: 都道府県会館, 東京
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Maternal experiences affect hippocampal neural plasticity (2014)
  • Author(s): Miyako Furuta, Atsushi Fukushima, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜, 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Relation between hippocampal sharp wave ripple events and prefrontal local field potential during delayed reinforcement task (2014)
  • Author(s): Sei-etsu Fujiwara, Yoshinori Izaki, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜, 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] The synchronized high frequency oscillation between the hippocampus and the amygdala during rest time after aversive stimuli in rats. (2014)
  • Author(s): Takafumi Kubota, Sei-etsu Fujiwara, Toshiya Funabashi, Tatsuo Akema
  • Organizer: The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜, 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Study on Glucose Metabolism via G-Protein-Coupled Estrogen Receptor 1 Expression In The Hypothalamus (2014)
  • Author(s): Atsushi Fukushima, Toshiya Funabashi, Tatsuo Akema
  • Organizer: 8th International Congress of Neuroendocrinology 2014
  • Place of Presentation: Hilton Sydney, Australia
  • Year and Date: 2014-08-17 – 2014-08-20
• [Presentation] エストロゲンの細胞膜エストロゲン受容体GPERを介した摂食調節機構に関する研究 (2014)
  • Author(s): Atsushi Fukushima, Toshiya Funabashi, Miyako Furuta, Hiomi Fujioka, Yuuji Ogura, Tatsuo Akema
  • Organizer: 第32回内分泌代謝学サマーセミナー
  • Place of Presentation: 富士レークホテル, 山梨
  • Year and Date: 2014-07-10 – 2014-07-12
• [Remarks] 生理学教室
  • URL: http://www.marianna-u.ac.jp/physiology/index.html
• [Remarks] 生理学教室
  • URL: http://seiri.webcrow.jp