Functional morphology of neuropeptide RLN3-survey for the involvement in emotion and food intake-

为了研究新的多肽松弛蛋白-3(RLN3)的功能，我们建立了基因敲除小鼠，并进行了一系列的行为测试。RLN3KO小鼠具有正常的生长和外观，通常与野生基因型的小鼠难以区分。不同基因型间体重差异不显著。然而，在高架加迷宫测试中，KO小鼠张开双臂的倾向表现出强劲的增长。因此，与野生型小鼠相比，RLN3 KO小鼠表现出温和的抗焦虑特征，这表明这种多肽参与了焦虑相关行为(Watanabe Y等人，Front Behav Neurosci 2011)。我们还通过脑室给药研究了RLN3对应激反应系统的下丘脑作用。侧脑室注射1nmolRLN3后，下丘脑室旁核(PVN)c-Fos表达增加。在含有CRF的神经元中，PVN前部的部分c-Fos被诱导。RLN3给药后15min，血浆ACTH水平也升高。这些结果表明，RLN3能够刺激下丘脑-垂体CRF-ACTH系统，在急性期对外部应激做出反应(Watanabe Y等，J Mol Neurosci 2011)。我写了一篇评论文章，从压力和食物摄入的角度总结了RLN3的功能(Tanaka M，FEBS J，2010)。

In order to investigate the function of newly peptide relaxin-3(RLN3), we have made gene knockout mice and examined a battery of the behavioral tests. RLN3 KO mice exhibited normal growth and appearance, and were generally indistinguishable from wild genotype littermates. There was no difference in bodyweight among genotypes. However, KO mice exhibited a robust increase in the tendency to enter open arms in the elevated plus maze test. Thus RLN3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior(Watanabe Y et al, Front Behav Neurosci 2011). We also investigated the hypothalamic action of RLN3 to stress-responding system by administrating it into the cerebral ventricle. RLN3 induced larger number of c-Fos expressions in the paraventricular nucleus of the hypothalamus(PVN) after 1nmol icv injection compared with saline injection. A part of c-Fos in the anterior PVN was induced in the CRF containing neurons. Plasma ACTH level was also increased 15 min after RLN3 administration. These results suggest that RLN3 is able to stimulate hypothalamo-pituitary CRF-ACTH system which responds to external stress in acute phase(Watanabe Y et al, J Mol Neurosci 2011). I wrote a review article to summarize the function of RLN3 in the view of stress and food intake(Tanaka M, FEBS J, 2010).