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Mediation of neuronal maturation and spinogenesis by PACAP signaling in primary hippocampal neurons

Research Project

Project/Area Number 25460100
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionOsaka University

Principal Investigator

HAYATA ATSUKO  大阪大学, 連合小児発達学研究科, 助教 (70390812)

Co-Investigator(Renkei-kenkyūsha) HASHIMOTO Hitoshi  大阪大学, 大学院薬学研究科, 教授 (30240849)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsPACAP / シナプス病態 / 精神疾患 / 樹状突起スパイン / 初代培養神経細胞 / セロトニン受容体 / 細胞内移行 / 神経細胞 / スパイン / 細胞内局在化
Outline of Final Research Achievements

Recent evidence implicates that abnormalities in dendritic spines are key substrates in the pathogenesis of several neuropsychiatric disorders. In this study, we analyzed the molecular mechanism for the spine maturation and spinogenesis by PACAP signaling. Here, we observed that miR-132 sponge and the MEK1/2 inhibitor U0126 blocked the PACAP-mediated increase in spine maturation and spinogenesis. In contrast, overexpression of miR-132 partly rescued the spine reductions in the PACAP-deficient primary neurons.
These data indicate that PACAP-miRNA132 signaling pathway is critically implicated in spine formation and contribute to understand the molecular mechanisms underlying neuropsychiatric disorders such as schizophrenia.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (36 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (20 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Int'l Joint Research] カリフォルニア大学ロサンゼルス校(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP).2015

    • Author(s)
      hibasaki Y, Hayata-Takano A, Hazama K, Nakazawa T, Shintani N, Kasai A, Nagayasu K, Hashimoto R, Tanida M, Katayama T, Matsuzaki S, Yamada K, Taniike M, Onaka Y, Ago Y, Waschek JA, Köves K, Reglődi D, Tamas A, Matsuda T, Baba A, Hashimoto H.
    • Journal Title

      Neuroscience

      Volume: 297 Pages: 95-104

    • DOI

      10.1016/j.neuroscience.2015.03.062

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p13 overexpression in pancreatic b-cells ameliorates type 2 diabetes in high-fat-fed mice2015

    • Author(s)
      Higashi, S. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 461 Issue: 4 Pages: 612-617

    • DOI

      10.1016/j.bbrc.2015.04.074

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder.2015

    • Author(s)
      Hashimoto R, Nakazawa T, Tsurusaki Y, Yasuda Y, Nagayasu K, Matsumura K, Kawashima H, Yamamori H, Fujimoto M, Ohi K, Umeda-Yano S, Fukunaga M, Fujino H, Kasai A, Hayata-Takano A, Shintani N, Takeda M, Matsumoto N, Hashimoto H.
    • Journal Title

      Journal of Human Genetics

      Volume: 61 Issue: 3 Pages: 199-206

    • DOI

      10.1038/jhg.2015.141

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative gene expression profiles in pancreatic islets associated with agouti yellow mutation and PACAP overexpression in mice2015

    • Author(s)
      Ikeda K, Tomimoto S, Tsuchiya S, Hamagami K, Shintani N, Sugimoto Y, Ichikawa A, Kasai A, Nakazawa T, Nagayasu K, Hayata-Takano A, Baba A, Hashimoto H
    • Journal Title

      Biochim Biophys Rep

      Volume: 2 Pages: 179-183

    • DOI

      10.1016/j.bbrep.2015.06.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PACAPシグナルによる精神神経機能調節におけるセロトニン2A受容体シグナルの関与2015

    • Author(s)
      Hayata A, Hazama K, Moriguchi K, Ago Y, Encho N, Nakazawa T, Nagayasu K, Kasai A, Onaka Y, Shintani N, Baba A, Hashimoto H.
    • Journal Title

      日本神経精神薬理学雑誌

      Volume: 35(2) Pages: 55-56

    • Related Report
      2015 Annual Research Report
  • [Journal Article] PACAP Enhances Axon Outgrowth in Cultured Hippocampal Neurons to a Comparable Extent as BDNF.2015

    • Author(s)
      Ogata K, Shintani N, Hayata-takano A, Kamo T, Higashi S, Seiriki K, Momosaki H, Vaudy D, Vaudy H, Galas L, Kasai A, Nagayasu K, Nakazawa T, Hashimoto R, Ago Y, Matsuda T, Baba A, Hashimoto H.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0120526-e0120526

    • DOI

      10.1371/journal.pone.0120526

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous neuron- and astrocyte-specific fluorescent marking.2015

    • Author(s)
      Schulze W, Hayata-Takano A, Kamo T, Nakazawa T, Nagayasu K, Kasai A, Seiriki K, Shintani N, Ago Y, Farfan C, Hashimoto R, Baba A, Hashimoto H.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 459 Issue: 1 Pages: 81-86

    • DOI

      10.1016/j.bbrc.2015.02.073

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice2015

    • Author(s)
      Yusuke Onaka, Norihito Shintani, Takanobu Nakazawa, Ryota Haba, Yukio Ago, Hyper Wang, Takuya Kanoh, Atsuko Hayata-Takano, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Ryota Hashimoto, Toshio Matsuda, James A. Waschek, Atsushi Kasai, Kazuki Nagayasu, Akemichi Baba, Hitoshi Hashimoto
    • Journal Title

      Behavioural Brain Research

      Volume: 284 Pages: 131-137

    • DOI

      10.1016/j.bbr.2015.02.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of the role of BMP and TGF-β signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro.2015

    • Author(s)
      Yamasaki A, Kasai A, Toi A, Kurita M, Kimoto S, Hayata-Takano A, Nakazawa T, Nagayasu K, Shintani N, Hashimoto R, Ito A, Meltzer HY, Ago Y, Waschek JA, Onaka Y, matsuda T, Baba A, Hashimoto H.
    • Journal Title

      Journal of Neurochemistry,

      Volume: 132(4) Issue: 4 Pages: 418-428

    • DOI

      10.1111/jnc.12999

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.2014

    • Author(s)
      Takuma K, Hara Y, Kataoka S, Kawanai T, Maeda Y, Watanabe R, Takano E, Hayata-Takano A, Hashimoto H, Ago Y, Matsuda T.
    • Journal Title

      Pharmacol Biochem Behav.

      Volume: 126 Pages: 43-49

    • DOI

      10.1016/j.pbb.2014.08.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Responses to a Hallucinogenic Drug in PACAP Heterozygous Mutant Mice.2014

    • Author(s)
      Hazama K, Hayata-Takano A, Uetsuki K, Kasai A, Encho N, Shintani N, Nagayasu K, Hashimoto R, Reglodi D, Miyakawa T, Nakazawa T, Baba A, Hashimoto H
    • Journal Title

      PLoS One

      Volume: 9(2)

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses psychomotor abnormalities and recognition memory deficits in mice lacking the pituitary adenylate cyclase-activating polypeptide.2013

    • Author(s)
      Ago Y
    • Journal Title

      Behavioural Pharmacology

      Volume: 24(1) Issue: 1 Pages: 74-77

    • DOI

      10.1097/fbp.0b013e32835cf3e5

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner.2013

    • Author(s)
      谷田守
    • Journal Title

      Neuroscience

      Volume: 238 Pages: 297-304

    • DOI

      10.1016/j.neuroscience.2013.02.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] マウス新生仔期VPAC2受容体活性化による感覚情報処理機能の障害2016

    • Author(s)
      吾郷 由希夫, Michael Condero, 早田 敦子, 河内 琢也, 橋本 均, James Waschek
    • Organizer
      日本薬学会大36年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 成熟雄性マウスの行動表現型ならびにシナプス関連たんぱく質発現に対するVPAC2受容体活性化の影響2016

    • Author(s)
      吾郷 由希夫, Michael Condero, 早田 敦子, 河内 琢也, 橋本 均, James Waschek
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] セロトニン神経機能に関わる遺伝子発現に対するmiRNAの作用2015

    • Author(s)
      大住 康晃, 永安 一樹, 笠井 淳司, 木本 早紀, 尾中 勇祐, 早田 敦子, 中澤 敬信,新谷 紀人, 橋本 均
    • Organizer
      第128回日本薬理学会近畿部会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪・豊中市)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Practical optimization of in situ hybridization procedure for the detection of microRNAs and mRNA expression in brain tissues2015

    • Author(s)
      Kasai A, Kakihara S, Okada R, Hazama K, Nakazawa T, Nagayasu K, Hayata-Takano A, Shintani N, Hashimoto H.
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      シカゴ(アメリカ)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] miRNAを介したPACAPによる樹状突起スパイン形成機構2015

    • Author(s)
      加茂 俊彦, 早田 敦子, 勢力 薫, 尾形 勝弥, 中澤 敬信, 永安 一樹, 笠井 淳司, 新谷 紀人, 橋本 均
    • Organizer
      第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
    • Place of Presentation
      タワーホール船堀(東京・江戸川区)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Overactivation of the VPAC2 receptor during postnatal brain maturation induces changes in synaptic proteins and selective alterations in prepulse inhibition in mice2015

    • Author(s)
      Ago Y, Hayata A, Kawanai T, Hashimoto H, Waschek J.
    • Organizer
      12th International Symposium on VIP/PACAP and Related Peptide
    • Place of Presentation
      カッパドキア(トルコ)
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of PACAP in depression-like behavior2015

    • Author(s)
      Hashimoto H, Shintani N, Ago Y, Hayata-Takano A, Waschek J, Baba A.
    • Organizer
      12th International Symposium on VIP/PACAP and Related Peptide
    • Place of Presentation
      カッパドキア(トルコ)
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Overactivation of the VPAC2 receptor during postnatal brain maturation induces changes in synaptic proteins and selective alterations in prepulse inhibition in mice2015

    • Author(s)
      吾郷 由希夫, 早田 敦子, 河内 琢也, 尾中 勇祐, 橋本 均, James Waschek.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティ(埼玉・大宮)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 慢性的な社会的敗北ストレスによる内側前頭前皮質におけるPACAP発現低下とエピジェネティクス関連因子の発現変化2015

    • Author(s)
      川瀬啓生、笠井淳司、小川純明、狭間啓佑、早田敦子、新谷紀人、馬場明道、橋本均
    • Organizer
      日本薬学会 第135年会
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 神経ペプチドPACAPによる精神機能調節:創薬への展望2014

    • Author(s)
      橋本均、新谷紀人、早田敦子、笠井淳司、永安一樹、中澤敬信
    • Organizer
      第36回日本生物学的精神医学会 第57回日本神経化学会大会 合同年会
    • Place of Presentation
      奈良県文化会館(奈良)
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] A crosstalk between PACAP and serotonin 2A signaling2014

    • Author(s)
      Moriguchi K, Hayata A, Michizoe H, Encho N, Shintani N, Baba A, Hashimoto H
    • Organizer
      20th International Symposium on Regulatory Peptides (REGPEG2014)
    • Place of Presentation
      京都ガーデンパレス(京都)
    • Year and Date
      2014-09-07 – 2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] コルチコステロン誘発性うつ病モデルを用いたプロスタノイド受容体DP2を介する情動制御機構の解析2014

    • Author(s)
      尾中勇祐、新谷紀人、木野村元彦、平井博之、長田欽也、中村正孝、早田敦子、笠井淳司、永安一樹、中澤敬信、馬場明道、橋本均
    • Organizer
      生体機能と創薬シンポジウム2014
    • Place of Presentation
      近畿大学薬学部 東大阪キャンパス(大阪)
    • Year and Date
      2014-08-28 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳内miRNA発現の高感度検出に向けたin situ hybridization法の最適化:炎症により発現変化する脳内miRNAの同定2014

    • Author(s)
      柿原素楽, 笠井淳司, 岡田遼, 狭間啓佑, 中澤敬信, 永安一樹, 早田敦子, 新谷紀人, 橋本均
    • Organizer
      生体機能と創薬シンポジウム2014
    • Place of Presentation
      近畿大学薬学部 東大阪キャンパス(大阪)
    • Year and Date
      2014-08-28 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] PACAP-PAC1 signaling pathway regulates internalization of serotonin 2A receptor in a PKC and b-arrestin2 dependent manner2014

    • Author(s)
      Hayata A, Moriguchi K, Encho N, Shintani N, Baba A, Hashimoto H
    • Organizer
      29th CINP World Congress of Neuropsychopharmacology
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2014-06-22 – 2014-06-26
    • Related Report
      2014 Research-status Report
  • [Presentation] PACAP-PAC1 signaling pathway regulates internalization of serotonin 2A receptor via a PKC and beta-arrestin2 dependent manner2014

    • Author(s)
      Atsuko Hayata, Keita Moriguchi, Naoki Encho, Toshihiko Kamo,t Norihito Shinani, Kazuki Nagayasu, Atsushi Kasai, Akemichi Baba, Hitoshi Hashimoto
    • Organizer
      29th CINP world congress of neuropsychopharmacology
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Altered expression of PACAP in the mPFC in depression-like states induced by chronic social defeat stress.2014

    • Author(s)
      Hazama K, Kasai A, Ogawa S, Hayata-Takano A, Shintani N, Baba A, Hashimoto H
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Vulnerability to a hallucinogenic drug in PACAP heterozygous mice is accompanied by altered neural response in the somatosensory cortex.2013

    • Author(s)
      Hazama K, Kasai A, Encho N, Hayata-Takano A, Shintani N, Baba A, Hashimoto H
    • Organizer
      Neuroscience2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] PACAP induces PKC-mediated serotonin 2A receptor internalization.2013

    • Author(s)
      Moriguchi K, Hayata-Takano A, Fujino T, Encho N, Nagayasu K, Kasai A, Shintani N, Baba A, Hashimoto H
    • Organizer
      第124回 日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] PACAP induces internalization of serotonin 2A receptor in a protein kinase C-dependent manner.2013

    • Author(s)
      Hayata-Takano A, Encho N, Moriguchi K, Fujino T, Shintani N, Kasai Baba A A, Hashimoto H
    • Organizer
      AsCNP2013
    • Place of Presentation
      Beijing, China
    • Related Report
      2013 Research-status Report
  • [Presentation] Analysis of PACAP signaling-mediated receptor internalization using the HaloTag system.2013

    • Author(s)
      Hayata-Takano A, Encho N, Moriguchi K, Fujino T, Shintani N, Kasai Baba A A, Hashimoto H
    • Organizer
      The 11th international symposium on VIP ,PACAP and related peptide
    • Place of Presentation
      Pecs, Hungary
    • Related Report
      2013 Research-status Report
  • [Remarks] 大阪大学大学院 薬学研究科 神経薬理学分野

    • URL

      http://molpharm.umin.jp/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 大阪大学大学院 連合小児発達学研究科 付属 子どものこころの分子統御機構研究センター

    • URL

      http://www.med.osaka-u.ac.jp/pub/kokoro/top.htm

    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2022-01-27  

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