The effect of antidepressant on Fibroblast growth factor (FGF) receptor, as a novel therapeutic target for major depression.

• Project/Area Number: 23790297
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Hiroshima University
• Principal Investigator: NAKASHIMA Kazue (HISAOKA Kazue) 広島大学, 大学院・医歯薬保健学研究院, 助教 (20393431)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 抗うつ薬 / グリア / 精神薬理学

Research Abstract

In this study, I examined the effect of amitriptyline (a tricyclic antidepressant) on the Fibroblast growth factor (FGF) receptor in glia. I reported that the amitriptyline-induced FGF receptor activation is occurred by FGF-2 shedding through matrix metalloproteinase activation (Hisaoka K et al., J Biol Chem 286(24): 21118-21128, 2011).

Research Products

• [Journal Article] Antidepressant acts on astrocytes leading to an increase in the expression of neurotrophic/growth factors: differential regulation of FGF-2 by noradrenaline (2012)
  • Author(s): Kajitani Naoto, Hisaoka-Nakashima Kazue, Morioka Norimitsu, Okada-Tsuchioka Mami, Kaneko Masahiro, Kasai Miho, Shibasaki Chiyo, Nakata Yoshihiro, Takebayashi Minoru.
  • Journal Title: PLoS One Volume: 7(12)
  • Peer Reviewed
• [Journal Article] Antidepressant Acts on Astrocytes Leading to an Increase in the Expression of Neurotrophic/ Growth Factors : Differential Regulation of FGF-2 by Noradrenaline (2012)
  • Author(s): N Kajitani, K Hisaoka-Nakashima, N Morioka, M Okada-Tsuchioka, M Kaneko, M Kasai, C Shibasaki, Y Nakata, M Takebayashi
  • Journal Title: PLOS ONE Volume: 7 Issue: 12 Pages: e51197-e51197
  • DOI: 10.1371/journal.pone.0051197
  • Peer Reviewed
• [Journal Article] Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. (2011)
  • Author(s): Hisaoka Kazue, Tsuchioka Mami, Yano Ryouya, Maeda Natsuko, Kajitani Naoto, Morioka Norimitsu, Nakata Yoshihiro, Takebayashi Minoru.
  • Journal Title: J Biol Chem Volume: 286(24) Pages: 21118-21128
  • Peer Reviewed
• [Journal Article] Riluzole-induced glial cell line-derived neurotrophic factor production is regulated through fibroblast growth factor receptor signaling in rat C6 glioma cells (2011)
  • Author(s): Tsuchioka Mami, Hisaoka Kazue, Yano Ryouya, Shibasaki Chiyo, Kajiatani Naoto, Takebayashi Minoru.
  • Journal Title: Brain Res Volume: 1384 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. (2011)
  • Author(s): Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M.
  • Journal Title: J Biol Chem. Volume: 286(24) Issue: 24 Pages: 21118-21128
  • DOI: 10.1074/jbc.m111.224683
  • Peer Reviewed
• [Journal Article] Riluzole-induced glial cell line-derived neurotrophic factor production is regulated through fibroblast growth factor receptor signaling in rat C6 glioma cells. (2011)
  • Author(s): Tsuchioka M, Hisaoka K, Yano R, Shibasaki C, Kajiatani N, Takebayashi M.
  • Journal Title: Brain Res. Volume: 1384 Pages: 1-8
  • DOI: 10.1016/j.brainres.2011.01.100
  • Peer Reviewed
• [Journal Article] Noradrenergic regulation of period1 expression in spinal astrocytes is involved in protein kinase A, c-Jun N-terminal kinase and extracellular signal-regulated kinase activation mediated by α1- and β2-adrenoceptors. (2011)
  • Author(s): Sugimoto T, Morioka N, Sato K, Hisaoka K, Nakata Y.
  • Journal Title: Neuroscience. Volume: 185 Pages: 1-13
  • DOI: 10.1016/j.neuroscience.2011.04.024
  • Peer Reviewed
• [Journal Article] Asymmetric alternation of the hemodynamic response at the prefrontal cortex in patients with schizophrenia during electroconvulsive therapy: a near-infrared spectroscopy study. (2011)
  • Author(s): Fujita Y, Takebayashi M, Hisaoka K, Tsuchioka M, Morinobu S, Yamawaki S.
  • Journal Title: Brain Res. Volume: 1410 Pages: 132-140
  • DOI: 10.1016/j.brainres.2011.06.052
  • Peer Reviewed
• [Journal Article] GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3
  • Author(s): Boku Shuken, Nakagawa Shin, Takamura Naoki, Kato Akiko, Takebayashi Minoru, Hisaoka-Nakashima Kazue, Omiya Yuki, Inoue Takeshi, Kusumi Ichiro.
  • Journal Title: Biochem Biophys Res Commun Volume: (in press)
  • Peer Reviewed
• [Presentation] 初代培養ラット大脳皮質アストロサイトにおいて三環系抗うつ薬アミトリプチリンはMEK/ERKカスケードを介してBDNF exon mRNAの発現を調節する (2013)
  • Author(s): 中島一恵
  • Organizer: Neuro2013
  • Place of Presentation: 京都市
• [Presentation] ラット初代培養アストロサイトにおいて抗うつ薬が BDNF exon mRNA 発現に及ぼす作用 (2012)
  • Author(s): 金子将大, 中島(久岡)一恵, 梶谷直人,葛西美穂, 重藤貴大, 森岡徳光, 竹林 実,仲田義啓
  • Organizer: 第121回日本薬理学会近畿部会
  • Place of Presentation: 徳島
  • Year and Date: 2012-06-29
• [Presentation] Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursor cells through inducing FGF2 secretion from astrocyte. (2012)
  • Author(s): Boku Shuken, Hisaoka-Nakashima Kazue, Nakagawa Shin, Kato Akiko, Kajitani Naoto, Inoue Takeshi, Takebayashi Minoru.
  • Organizer: 51th annual meeting of ACNP
  • Place of Presentation: Florida U.S.A.
• [Presentation] 三環系抗うつ薬Amitriptyline によるグリア細胞株由来神経栄養因子(GDNF)産生機構におけるマトリックスメタロプロテアーゼ(MMP)の関与 (2012)
  • Author(s): 中島(久岡)一恵, 矢野遼也, 安部裕美,岡田麻美, 柴崎千代, 梶谷直人, 森岡徳光,竹林 実, 仲田義啓
  • Organizer: 第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 宇都宮
• [Presentation] Distinct regulation of fibroblast growth factor-2 expression by antidepressant and noradrenaline in rat cortical astrocytes (2012)
  • Author(s): Kajitani Naoto, Hisaoka-Nakashima Kazue, Morioka Norimitsu, Okada-Tsuchioka Mami, Shibasaki Chiyo, Kaneko Masahiro, Kasai Miho, Nakata Yoshihiro, Takebayashi Minoru
  • Organizer: 42th Annual Meeting of Society for Neuroscience
  • Place of Presentation: New Orleans U.S.A
• [Presentation] ラット大脳皮質アストロサイトにおいて、amitriptyline による FGF-2の発現は複数の受容体型チロシンキナーゼを介して調節される (2012)
  • Author(s): 細井茉由, 岡田麻美, 梶谷直人, 矢野遼也, 柴崎千代, 久岡一恵, 森岡徳光, 仲田義啓, 竹林 実
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
• [Presentation] 抗うつ薬がラット初代培養アストロサイトの BDNF exon mRNA の発現に及ぼす効果 (2012)
  • Author(s): 金子将大, 久岡一恵, 梶谷直人, 葛西美穂, 岡田麻美, 森岡徳光, 竹林 実, 仲田義啓
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
• [Presentation] 三環系抗うつ薬Amitriptylineによるグリア細胞株由来神経栄養因子(GDNF)産生機構におけるマトリックスメタロプロテアーゼ(MMP)の関与 (2012)
  • Author(s): 中島（久岡）一恵
  • Organizer: 第22回日本臨床精神神経薬理学会・第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 宇都宮市
• [Presentation] 抗うつ薬によるグリア細胞株由来神経栄養因子(GDNF) 産生機構の解明:マトリックスメタロプロテアーゼ(MMP)の関与 (2011)
  • Author(s): 矢野遼也, 久岡一恵, 細井茉由, 岡田麻美, 柴崎千代, 梶谷直人, 森岡徳光, 竹林 実, 仲田義啓
  • Organizer: 第120回日本薬理学会近畿部会
  • Place of Presentation: 京都
  • Year and Date: 2011-11-11
• [Presentation] 抗うつ薬は初代培養アストロサイトから FGF-2 を産生する (2011)
  • Author(s): 梶谷直人, 久岡一恵, 金子将大, 葛西美穂, 矢野遼也, 岡田麻美, 竹林 実, 森岡徳光, 仲田義啓
  • Organizer: 第119回日本薬理学会近畿部会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-08
• [Presentation] Antidepressants activate expression of fibroblast growth factor receptor (FGFR) signaling in glial cells: Involvement in glial cell line-derived neurotrophic factor (GDNF) production (2011)
  • Author(s): Hisaoka Kazue, Okada-Tsuchioka Mami, Yano Ryouya, Kajitani Naoto, Morioka Norimitsu, Nakata Yoshihiro, Takebayashi Minoru.
  • Organizer: 41th Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington DC U.S.A.
• [Presentation] Electroconvulsive seizure (ECS) increases thrombospondin-1 (TSP-1) expression in the adult rat hippocampus. (2011)
  • Author(s): Okada-Tsuchioka Mami, Takebayashi Minoru, Segawa Masashi, Hosoi Mayu, Kajitani Naoto, Shibasaki Chiyo, Yano Ryouya, Hisaoka Kazue, Morinobu Shigeru
  • Organizer: 41th Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington DC U.S.A.
• [Presentation] Antidepressants activate expression of fibroblast growth factor receptor (FGFR) signaling in glial cells: Involvement in glial cell line-derived neurotrophic factor (GDNF) production. (2011)
  • Author(s): Hisaoka Kazue, Takebayashi Minoru, Okada-Tsuchioka Mami, Yano Ryouya, Kajitani Naoto, Morioka Norimitisu, Nakata Yoshihiro.
  • Organizer: 2nd Congress of Asian College of Neuropsychopharmacology Jointly with 2011 Annual Meeting of KCNP
  • Place of Presentation: Seoul Korea
• [Presentation] The increase of FGF-2 expression by amitryptyline and noradrenaline could be mediated different mechanisms in rat primary cultured astrocytes. (2011)
  • Author(s): Kajitani Naoto, Hisaoka Kazue, Kaneko Masahiro, Kasai Miho, Yano Ryouya, Okada-Tsuchioka Mami, Morioka Norimitsu, Takebayashi Minoru, Nakata Yoshihiro.
  • Organizer: 2nd Congress of Asian College of Neuropsychopharmacology Jointly with 2011 Annual Meeting of KCNP
  • Place of Presentation: Seoul Korea
• [Presentation] 抗うつ薬は初代培養アストロサイトからFGF-2を産生する (2011)
  • Author(s): 梶谷直人、久岡一恵、金子将大、葛西美穂、矢野遼也、岡田麻美、竹林 実、森岡徳光、仲田義啓
  • Organizer: 第119回日本薬理学会近畿部会
  • Place of Presentation: 名古屋市
• [Presentation] 抗うつ薬によるグリア細胞株由来神経栄養因子(GDNF)産生機構の解明：マトリックスメタロプロテアーゼ(MMP)の関与 (2011)
  • Author(s): 矢野遼也、久岡一恵、細井茉由、岡田麻美、柴崎千代、梶谷直人、森岡徳光、竹林 実、仲田義啓
  • Organizer: 第120回日本薬理学会近畿部会
  • Place of Presentation: 京都市
• [Presentation] ラット初代培養アストロサイトにおいて抗うつ薬がBDNF exon mRNA発現に及ぼす作用
  • Author(s): 金子将大
  • Organizer: 第121回日本薬理学会近畿部会
  • Place of Presentation: 徳島市
• [Presentation] Distinct regulation of fibroblast growth factor-2 expression by antidepressant and noradrenaline in rat cortical astrocytes
  • Author(s): Naoto Kajitani
  • Organizer: 42th Annual Meeting of Society for Neuroscience
  • Place of Presentation: New Orleans, USA
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/pha/
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/pha/sub1.html