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

利用其特异性受体PAC1转基因小鼠分析PACAP的脑功能。

• 批准号: 19500368
• 负责人: ARATA Satoru
• 金额: $ 2.5万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19500368/
• 关键词: 病態モデル; PACAP; トランスジェニックマウス; 行動解析; 発生工学; 高次神経機能; 行動生理; PAC1; 学習・記憶; サーカディアン

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.

为了明确垂体腺苷酸环化酶激活多肽（PACAP）的生理功能，我们利用Cre/loxP重组系统建立了PACAP偏好受体（PAC 1）转基因（Tg）小鼠。本实验通过建立PAC 1转基因小鼠模型，研究了PAC 1转基因小鼠脑内PACAP的生理功能。在笼内自发运动活动，PAC 1表达，特别是在海马中，增加了早期黑暗期（ZT 12-17）的行为活动，这是野生型小鼠最活跃的时间段。此外，在通常抑制运动活动的老年小鼠中，hPAC 1 Tg小鼠表现出更活跃的时钟式昼夜节律。这些结果表明，PAC 1转基因的表达，特别是在海马神经细胞，使增强的行为活动与规则的昼夜节律。另一方面，我们研究了PACAP在发育呼吸适应的影响，全身体积描记法和离体分析使用脑干脊髓准备。尽管这一研究还很原始，但目前认为PACAP信号通路与中枢呼吸节律的形成有关。

项目成果

Impaired mast cell maturation and degranulation and attenuated allergic responses inndrgl-deficient mice.

缺乏ndrgl的小鼠肥大细胞成熟和脱颗粒受损，过敏反应减弱。

• 发表时间: 2007
• 期刊: J. Immunol. 178
• 作者: Taketomi;Y.;Sunaga;K.;Tanaka;S.;Nakamura;M.;Arata;S.;Okuda;T.;Moon;T.C.;Chang;H.W.;Sugimoto;Y.;Kokame;K.;Miyata;T.;Murakami;M.;and Kudo;I.
• 通讯作者: I.

Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice

• DOI: 10.1161/atvbaha.108.164723
• 发表时间: 2009-01-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Kato, Rina;Mori, Chihiro;Itabe, Hiroyuki
• 通讯作者: Itabe, Hiroyuki

Occurrence of central respiratory failure in mouse model depend on host genetic background

小鼠模型中枢性呼吸衰竭的发生取决于宿主遗传背景

• 发表时间: 2009
• 作者: Arata S;Amano K;Yamakawa K;Arata A
• 通讯作者: Arata A

Defective interaction between dual oscillators for respiratory rhythm generation in Na^+, K^+-ATPase alpha2 subunit-deficient mice

Na^、K^-ATPase α2 亚基缺陷小鼠双振荡器之间的相互作用有缺陷，导致呼吸节律产生

• 发表时间: 2007
• 期刊: J.Physiol 584
• 作者: Ikeda;K.;Onimaru H.
• 通讯作者: Onimaru H.

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

小鼠脑缺血模型分析内源性PACAP对神经元细胞死亡的抑制作用

• 发表时间: 2009
• 作者: 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
• 通讯作者: 塩田清二