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

为了明确垂体腺苷环化酶激活多肽(PACAP)的生理作用，我们利用Cre/loxP重组系统建立了PACAP偏好受体(PAC1)转基因(TG)小鼠。获得了在全身(wPAC1TG小鼠)、海马区(hPAC1TG小鼠)和三苯氧胺治疗后的海马区(ihPAC1TG小鼠)表达PAC1转基因的三种类型的PAC1TG小鼠。家笼自发活动，PAC1的表达，尤其是在海马区，增加了行为活动的早期黑暗时期(ZT12-17)，这是最活跃的时区的野生型小鼠。此外，在普遍抑制运动活动的老年小鼠中，hPAC1转基因小鼠表现出更活跃的昼夜节律。这些结果表明，转基因PAC1的表达，特别是在海马神经细胞中的表达，使行为活动增强，具有规律的昼夜节律。另一方面，我们通过全身体积图和脑干-脊髓标本的体外分析，研究了PACAP在发育性呼吸适应中的作用。尽管该研究尚处于起步阶段，但到目前为止，已有研究表明PACAP信号与中枢呼吸节律的发生有关。

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.