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Analysis of the central respiratory disorder in PACAP-deficient mice

Research Project

Project/Area Number 22500390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionShowa University

Principal Investigator

ARATA Satoru  昭和大学, 遺伝子組換え実験室, 准教授 (20159502)

Co-Investigator(Kenkyū-buntansha) ONIMARU Hiroshi  昭和大学, 医学部, 准教授 (30177258)
NAKAMACHI Tomoya  昭和大学, 遺伝子組換え実験室, 助教 (30433840)
畠 あずさ  昭和大学, 動物実験施設, 技術員 (20568290)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords乳幼児突然死症候群(SIDS) / 呼吸中枢障害マウスモデル / Pituitary adenylate cyclase activating polypeptide(PACAP) / SIDS / PACAP / 呼吸中枢 / 低酸素受容体 / 中枢性呼吸疾患 / 疾患モデルマウス
Research Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide expressed widely in nervous tissues. PACAP knockout (-/-) mice display a sudden infant death syndrome (SIDS)-like phenotype, although the underlying physiological mechanism to explain this remains unclear. Here, we reporton the presence of abnormal respiratory activity in PACAP -/- mice under hypoxic conditions, which provides a basis for the SIDS-like phenotype. PACAP -/- mice display a lowered baseline respiratory activity compared with wild-type animals, and an abnormal response to hypoxia. Histological and real time PCR analyses indicated that the catecholaminergic system in the medulla was impaired in PACAP-/- mice, suggesting that endogenous PACAP affects respiratory centers in the medulla via its action on the catecholaminergic system. We propose that disruption of this system may beinvolved in the sudden infant death-like phenotype of PACAP -/- mice. Thus, disorders of the catecholaminergic system involved with O_2sensing could be implicated in underlying neuronal mechanisms responsible for SIDS.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2013 2012 2011 2010

All Journal Article (17 results) (of which Peer Reviewed: 8 results) Presentation (23 results) Book (3 results)

  • [Journal Article] Impaired response to hypoxia in therespiratory center is a major cause of neonatal death of the PACAP-knockout mouse2013

    • Author(s)
      ArataS, Nakamachi T, Onimaru H, Hashimoto H, Shioda S
    • Journal Title

      Eur J Neurosci

      Volume: 37(3) Pages: 407-16

    • Related Report
      2012 Final Research Report
  • [Journal Article] Impaired response to hypoxia in the respiratory center is a main cause of neonatal death of the PACAP knockout mouse2013

    • Author(s)
      Arata Satoru, Nakamachi, Tomoya,Onimaru Hiroshi, Hashimoto Hitoshi and Shioda Seiji
    • Journal Title

      European Journal of Neuroscience

      Volume: 37 Issue: 3 Pages: 407-416

    • DOI

      10.1111/ejn.12054

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcium imaging of neuronal activity in the most rostral parafacial respiratory group of the newborn rat2012

    • Author(s)
      Onimaru H and Dutschmann M
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 62 Pages: 71-77

    • NAID

      10030351499

    • Related Report
      2012 Final Research Report
  • [Journal Article] Postsynaptic mechanisms of CO_2responses in parafacial respiratory neurons of newborn rats2012

    • Author(s)
      Onimaru H, Ikeda K and Kawakami K.
    • Journal Title

      J Physiol

      Volume: 590 Pages: 1615-1624

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-6 and PACAP receptor expression and localization after global brain ischemia in mice2012

    • Author(s)
      Nakamachi T, Tsuchida M, Kagami N, Yofu S, Wada Y, Hori M, Tsuchikawa D, Yoshikawa A, Imai N, Nakamura K, ArataS, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 48(3) Pages: 518-25

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-6 and PACAP receptor expression and localization after global brain ischemia in mice.2012

    • Author(s)
      NAKAMACHI Tomoya
    • Journal Title

      J Mol Neurosci

      Volume: 48 Pages: 518-525

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postsynaptic mechanisms of CO2 responses in parafacial respiratory neurons of newborn rats2012

    • Author(s)
      ONIMARU Hiroshi
    • Journal Title

      J Physiol.

      Volume: 590 Pages: 1615-1624

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro2011

    • Author(s)
      Nakamachi T, Nakamura K, Oshida K, Kagami N, Mori H, Watanabe J, Arata S, Yofu S, Endo K, Wada Y, Hori M, Tsuchikawa D, Kato M, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43 Pages: 16-21

    • Related Report
      2012 Final Research Report
  • [Journal Article] Role of PACAP in neural stem/progenitor cell and astrocyte - from neural development to neural repair2011

    • Author(s)
      Nakamachi T, Farkas J, Watanabe J, Ohtaki H, Dohi K, ArataS, Shioda S.
    • Journal Title

      Curr Pharm Des

      Volume: 17(10) Pages: 973-84

    • Related Report
      2012 Final Research Report
  • [Journal Article] Dietary cholesterol reduces plasma triacylglycerol in apolipoprotein E-null mice: suppression of lipin-1 and -2 in the glycerol-3-phosphate pathway2011

    • Author(s)
      Obama T, Nagaoka S, Akagi K, Kato R, Horiuchi N, Horai Y, Aiuchi T, ArataS, Yamaguchi T, Watanabe M, Itabe H
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2012 Final Research Report
  • [Journal Article] m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis2011

    • Author(s)
      Miyazaki T, Taketomi Y, Takimoto M, Lei XF, Arita S, Kim-Kaneyama JR, ArataS, Ohata H, Ota H, Murakami M, Miyazaki A
    • Journal Title

      Circulation

      Volume: 124 (23) Pages: 2522-32

    • Related Report
      2012 Final Research Report
  • [Journal Article] m-Calpain is induced in vascular endothelial cells on human atheroma and accelerates atherosclerotic lesion development through proteolytic disorganization of VE-cadherin in hypercholesterolemic mice2011

    • Author(s)
      Miyazaki, T., Taketomi, Y., Takimoto, M., Lei, X., Akita, S., Kim-Kaneyama, J., Arata, S., Ohata, H., Ota, H., Murakami, M., and Miyazaki, A.
    • Journal Title

      Circulation

      Volume: 124 Issue: 23 Pages: 2522-2532

    • DOI

      10.1161/circulationaha.111.021675

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of PACAP in neural stem/progenitor cell and astrocyte-from neural development to neural repair2011

    • Author(s)
      Nakamachi Tomoya
    • Journal Title

      Curr Pharm Des

      Volume: 17 Pages: 973-984

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Identification and Isolation of Neural Crest Derived Cells in Nasal Concha2011

    • Author(s)
      Ono Miki
    • Journal Title

      Jpn.J.Tissue Cult.Dent.Res.

      Volume: 20 Pages: 29-35

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dietary cholesterol reduces plasma triacylglycerol in apolipoprotein E-null mice : Suppression of lipin-1 and -2 in the glycerol-3-phosphate2011

    • Author(s)
      Takashi Obama, et al
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 8 Pages: 22917-22917

    • DOI

      10.1371/journal.pone.0022917

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro.2011

    • Author(s)
      NAKAMACHI Tomoya
    • Journal Title

      J Mol Neurosci

      Volume: 43 Pages: 16-21

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice.2010

    • Author(s)
      SATO Hirotasu
    • Journal Title

      J Clin Invest.

      Volume: 120

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウスにおけるPACAPの角膜傷害治癒効果の検討2013

    • Author(s)
      中町 智哉
    • Organizer
      第118回日本解剖学会総会・全国学術集会
    • Place of Presentation
      香川
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脳虚血後のマウス海馬におけるIL-6とPACAP受容体の発現動態2013

    • Author(s)
      中町 智哉
    • Organizer
      第118回日本解剖学会総会・全国学術集会
    • Place of Presentation
      香川
    • Related Report
      2012 Annual Research Report
  • [Presentation] PACAP 誘導性の涙液分泌におけるアクアポリン5の役割2012

    • Author(s)
      中町智哉、会沢洋一、大滝博和、養父佐知子、関 保、和田悦洋、荒田 悟、新谷紀人、橋本 均、馬場明道、塩田清二
    • Organizer
      第117回日本解剖学会総会・全国学術集会
    • Place of Presentation
      甲府
    • Related Report
      2012 Final Research Report
  • [Presentation] PACAP欠損マウスにおける中枢性呼吸異常2012

    • Author(s)
      荒田 悟、中町智哉、鬼丸 洋、橋本 均、塩田清二
    • Organizer
      第9回GPCR研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] PACAP KOマウスにおける中枢性呼吸異常の解析2012

    • Author(s)
      荒田 悟、中町智哉、鬼丸 洋、塩田 清二
    • Organizer
      第59回日本実験動物学会総会
    • Place of Presentation
      別府
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] PACAP stimulates tear secretion in mouse2012

    • Author(s)
      NAKAMACHI Tomoya
    • Organizer
      19th International Symposium on Regulatory Peptides
    • Place of Presentation
      Denmark
    • Related Report
      2012 Annual Research Report
  • [Presentation] PACAP suppresses retinal neuronal damage through modulation of the activation state of retinal microglia/macrophage2012

    • Author(s)
      NAKAMACHI Tomoya
    • Organizer
      The 42th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] PACAP STIMULATES THE LACRIMATION VIA AQUAPORIN 5 TRANSLOCATOIN IN MOUSE2011

    • Author(s)
      NAKAMACHI tomoya
    • Organizer
      The 10th international Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Eilat Israel
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on reactive astrocyte induced by brain damage in mice2011

    • Author(s)
      NAKAMACHI tomoya
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Expressin of pituitary adenylate cyclase-activating polpeptide (PACAP) receptor on reactive astrocyte after brain ischemia inmice2011

    • Author(s)
      NAKAMACHI tomoya
    • Organizer
      Brain edema 2011 ; The XVth International Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-10-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] The differences of the respiratory network between C57BL/6 and Balb/c in Dscam knock out mice2011

    • Author(s)
      ARATA Akiko
    • Organizer
      The 34th Annual Meeting of the JNS
    • Place of Presentation
      Yokohama
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 涙液分泌機能低下を示すPACAP欠損マウスを用いた涙液分泌機構の解析2011

    • Author(s)
      中町智哉
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] PACAP欠損マウスに見られた新生児期の呼吸異常の解析2011

    • Author(s)
      荒田悟
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] C57BL/6マウス飼育における環境エンリッチメントの導入:行動学的評価2011

    • Author(s)
      畠あずさ
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] PACAP遺伝子欠損マウスにおける呼吸機能異常2011

    • Author(s)
      中町智哉
    • Organizer
      第88回日本生理学会大会・第116回日本解剖学会総会・全国学術集会 合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] PACAP遺伝子欠損マウスにおける呼吸機能異常Abnormality of respiratory function in PACAP knockout mouse2011

    • Author(s)
      中町智哉、荒田 悟、鬼丸 洋、塩田 清二
    • Organizer
      第88回日本生理学会/第116回日本解剖学会・学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Distribution of activity-dependent neuroprotective protein (ADNP) and PAC1 receptor in intact and ischemic mouse brain.2010

    • Author(s)
      NAKAMACHI Tomoya
    • Organizer
      The 40th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2010-10-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] Morphological analysis of galanin-like peptide (GALP)-producing cells using a line of transgenic mice that expresses fluorescent protein under the control of mouse transcription regulatory regions of GALP.2010

    • Author(s)
      Kageyama Haruaki
    • Organizer
      XI International Congress of Obesity (ICO2010)
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2010-07-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規ドライアイ疾患モデル動物としてのPACAP遺伝子欠損マウスの評価2010

    • Author(s)
      中町智哉
    • Organizer
      第57回日本実験動物学会総会
    • Place of Presentation
      京都
    • Year and Date
      2010-05-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新生マウス呼吸馴化における低酸素および高二酸化炭素環境に対する応答性2010

    • Author(s)
      荒田 悟、中町智哉、鬼丸 洋、荒田晶子、塩田清二
    • Organizer
      第57回日本実験動物学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] 新規ドライアイ疾患モデル動物としてのPACAP 遺伝子欠損マウスの評価2010

    • Author(s)
      中町智哉、会沢洋一、大滝博和、関 保、遠藤貴美、荒田 悟、新谷紀人、橋本均、馬場明道、塩田清二
    • Organizer
      第57回日本実験動物学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] C57BL/6マウス飼育における環境エンリッチメントの導入:繁殖と発育への影響2010

    • Author(s)
      畠あずさ、中町智哉、荒田 悟、塩田清二
    • Organizer
      第57回日本実験動物学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] 顎顔面口腔組織における神経堤由来細胞の分布解析とそれを用いた骨芽細胞様細胞の分化誘導2010

    • Author(s)
      小野美樹、高見正道、須澤徹夫、宮内知彦、林 竜平、荒田 悟、細野知彦、馬場一美、中村雅典、槇宏太郎、西田幸二、大隅典子、上條竜太郎
    • Organizer
      第47回日本口腔組織培養学会
    • Place of Presentation
      高知
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Book] Role of PACAP in neural stem/progenitor cell and astrocyte - from neural development to neural repair, Curr Pharm Des2011

    • Author(s)
      Nakamachi T, Farkas J, Watanabe J, Ohtaki H, Dohi K, Arata S, Shioda S
    • Related Report
      2012 Final Research Report
  • [Book] Central respiratory failure in a mouse model depends on the genetic background of the host, Adv Exp Med Biol2010

    • Author(s)
      Arata S, Amano K, Yamakawa K, Arata A
    • Related Report
      2012 Final Research Report
  • [Book] Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency. Adv Exp Med Biol2010

    • Author(s)
      Amano K, Fujii M, Arata S, Ogawa M, Yamakawa K, and Arata A
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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