Analysis of brain functions of PACAP using its specific receptor PAC1 transgenic mice.

2009 Fiscal Year Final Research Report

• Project/Area Number: 19500368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Showa University
• Principal Investigator: ARATA Satoru Showa University, 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) ; TAKETOMI Yoshitaka 昭和大学, 遺伝子組換え実験室, 助教 (40365804)
• Project Period (FY): 2007 – 2009
• Keywords: 病態モデル

Research Abstract

To define the physiological roles of pituitary adenylate cyclase-activating polypeptide (PACAP), we developed the PACAP-preferring receptor (PAC1) transgenic (Tg) mice using the Cre/loxP recombination system. The three type of PAC1 Tg mice which were expressed the Pac1 transgene in the whole body (wPAC1 Tg mice), in the hippocampus (hPAC1 Tg mice), and in the hippocampus after tamoxifen treatment (ihPAC1 Tg mice), were obtained.
We studied here the physiological roles of PACAP in brain using these PAC1 Tg mice. The spontaneous motor activity in home cage, the PAC1 expression, especially in hippocampus, increased behavioral activity at early dark period (ZT 12-17) which is most active time zone of the wild type mice. Furthermore, on the aged-mice which generally depressed motor activity, hPAC1 Tg mice showed more active with a clockwork circadian rhythm. These results suggest that the expression of PAC1 transgene, especially in the hippocampus nerve cells, make to enhance the behavioral activity with regular circadian rhythm. On the other hand, we studied the effect of PACAP in developmental respiratory adaptation by whole-body plethysmography and ex vivo analysis using brainstem-spinal cord preparation. Although this study is primitive, up to now, it was suggested that PACAP signaling concerned the development of central respiratory rhythmgensis.

Research Products

• [Journal Article] Central respiratory failure in a mouse model depends on the genetic background of the host. (2010)
  • Author(s): Arata S, Amano K, Yamakawa K, Arata A.
  • Journal Title: Adv Exp Med Biol. 669 Pages: 21-24
• [Journal Article] Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency (2010)
  • Author(s): Amano K, Fujii M, Arata S, Ogawa M, Yamakawa K, Arata A
  • Journal Title: Adv Exp Med Biol. 669 Pages: 15-19
• [Journal Article] Transient increase in plasma oxidized LDL during the progression of atherosclerosis in apolipoprotein E knockout mice. (2009)
  • Author(s): Kato R, Mori C, Kitazato K, Arata S, Obama T, Mori M, Takahashi K, Aiuchi T, Takano T, Itabe H.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(1) Pages: 33-9
  • Peer Reviewed
• [Journal Article] Arata SDSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death. (2009)
  • Author(s): Amano K, Fujii M, Tojima T, Ogawa M, Morita N, Shimohata A, Furuichi T, Itohara S, Kamiguchi H, Korenberg JR, Arata A, Yamakawa K.
  • Journal Title: J Neurosci. 29(9) Pages: 2984-96
  • Peer Reviewed
• [Journal Article] Arata SDepletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice. (2009)
  • Author(s): Imai H, Hakkaku N, Iwamoto R, Suzuki J, Suzuki T, Tajima Y, Konishi K, Minami S, Ichinose S, Ishiizaka K, Shioda S, Nishimura M, Naito S, Nakagawa Y.
  • Journal Title: J Biol Chem. 284(47) Pages: 32522-32
  • Peer Reviewed
• [Journal Article] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using ghrelin-EGFP transgenic mice. (2008)
  • Author(s): Kageyama, H, Kitamura, Y, Hosono, T, Kintaka, Y, Seki, M, Takenoya, F, Hori, Y, Nonaka, N, Arata, S, Shioda, S
  • Journal Title: Regul Pept. 145 Pages: 116-21
  • Peer Reviewed
• [Journal Article] Arata S Generation of muscle aquaporin 4 overexpressing transgenic mouse: Its characterization at RNA and protein levels including freeze-fracture study. (2007)
  • Author(s): Wakayama Y, Takahashi J, Shibuya S, Inoue M, Kojima H, Oniki H, Hara H, Jimi T, Shioda S, Sunada Y, Ohi H, Shimizu T.
  • Journal Title: Micron. Micron. 38(3) Pages: 257-267
  • Peer Reviewed
• [Journal Article] Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice. (2007)
  • Author(s): Taketomi YTanaka S, Sunaga K,, Nakamura M, Arata S, Okuda T, Moon TC, Chang HW, Sugimoto Y, Kokame K, Miyata T, Murakami M, Kudo I.
  • Journal Title: J Immunol. 178(11) Pages: 7042
  • Peer Reviewed
• [Presentation] DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death (2009)
  • Author(s): Amano K, Fujii M, Arata S, Yamakawa K, Arata A
  • Organizer: 11th Oxford
  • Place of Presentation: Nara
  • Year and Date: 20090700
• [Presentation] Occurrence of central respiratory failure in mouse model depend on host genetic background (2009)
  • Author(s): Arata S, Amano K, Yamakawa K, Arata A
  • Organizer: 11th Oxford
  • Place of Presentation: Nara
  • Year and Date: 20090700
• [Presentation] 新生期マウスの呼吸馴化における系統の差異 (2009)
  • Author(s): 荒田悟、荒田晶子、武富芳隆、細野知彦、鬼丸洋、塩田清二
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 大宮
  • Year and Date: 20090500
• [Presentation] マウス脳虚血モデルを用いた内因性PACAPの神経細胞死抑制作用の解析 (2009)
  • Author(s): 中町智哉、大滝博和、養父佐知子、野中直子、荒田悟、William A. Banks、塩田清二
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 大宮
  • Year and Date: 20090500
• [Presentation] PACAP特異的受容体(PAC1)トランスジェニックマウスにおける自発行動の亢進 (2008)
  • Author(s): 荒田悟、細野知彦、武富芳隆、影山晴秋、中町智哉、塩田清二
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 20081200
• [Presentation] III型ホスホリパーゼA2は即時型アレルギーに関与する (2008)
  • Author(s): 武富芳隆、川名桃子、佐藤弘泰、田中智之、山本圭、荒田悟、原俊太郎、工藤一郎、村上誠
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 20081200
• [Presentation] III型分泌性ホスホリパーゼA2は即時性アレルギーに関与する (2008)
  • Author(s): 武富芳隆、川名桃子、佐藤弘泰、田中智之、上野紀子、山本圭、荒田悟、原俊太郎、工藤一郎、村上誠
  • Organizer: 第9回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20080600
• [Presentation] Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1) transgenic mice. (2008)
  • Author(s): S. Arata, T. Hosono, Y. Taketomi, H. Kageyama, T. Nakamachi, S. Shioda.
  • Organizer: 5th Showa International Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2008-09-02
• [Presentation] Visualization of ghrelin-producing neurons in the hypothalamic arcuate nucleus using the ghrelin-enhanced green fluorescent protein transgenic mice. (2007)
  • Author(s): Kageyama H, Hosono T, Arata S, Takenoya F, Shioda S.
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 20071103-20071107
• [Presentation] Loss of Pre-inspiratory neuron synchroneity in mice with Dscam1 deficiency. (2007)
  • Author(s): Amano K, Fujii M, Tojima T, Ogawa M, Morita N, Arata S, Shimohata A, Furuichi T, Itohara S, Kamiguchi H, J R Korenberg, Arata A, Yamakawa K
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 20071103-20071107
• [Presentation] 膜結合型Ca2+非依存性ホスホリパーゼA2(iPLA2γ)の解析 (2007)
  • Author(s): 依田恵美子、小林裕司、藤本知佳子、桑田浩、武富芳隆、荒田悟、中谷良人、原俊太郎、工藤一郎
  • Organizer: 第49回日本脂質生化学会
  • Place of Presentation: 北海道
  • Year and Date: 20070600
• [Presentation] マスト細胞の成熟に伴って発現誘導されるNDRG1の解析 (2007)
  • Author(s): 武富芳隆、須永剛平、田中智之、中村雅典、荒田悟、奥田智彦、杉本幸彦、小亀浩市、宮田敏行、村上誠、工藤一郎
  • Organizer: 第8回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 20070600
• [Presentation] PACAP受容体(PAC1)トランスジェニックマウスにおける自発行動の亢進について (2007)
  • Author(s): 荒田悟、影山晴秋、中町智哉、武富芳隆、細野知彦、塩田清二
  • Organizer: 第54回日本実験動物学会総会
  • Place of Presentation: 東京
  • Year and Date: 20070500
• [Book] Transmitters and Modulators in Heaith and Disease(S. Shioda, I. Homma, N. Kato editors., Increased behavioral activity with regular circadian rhythm in PACAP specific receptor (PAC1) transgenic mice) (2009)
  • Author(s): Arata S, Hosono T, Taketomi Y, Kageyama H, Nakamachi T, Shioda S.
  • Total Pages: 199-205
  • Publisher: Springer-Verlag