INVESTIGATION ON PHYSIOLOGICAL ROLE OF BOMBESIN-LIKE PEPTIDE RECEPTOR SYSTEM IN BRAIN

在这项研究中，我们旨在阐明蛙皮素样肽受体在哺乳动物大脑中的生理作用。以前的研究表明，该系统参与了不同的生物学方面，然而，每个蛙素样肽受体在这些方面的单独作用仍然难以捉摸。我们建立了三种哺乳动物蛙皮素样肽受体的基因敲除小鼠，它们是胃泌素释放肽受体(GRPR)、神经介素B受体(NMBR)和蛙皮素受体亚型3(Brs3)。对基因敲除小鼠的行为分析表明，GRPR基因敲除小鼠表现出更多的社会反应和社会调查行为。由于镇静剂的治疗不会改变GRPR基因敲除小鼠的反应，GRPR基因敲除小鼠的社交活动增加不太可能是由改变的焦虑引起的。相反，基因敲除小鼠的行为被认为是气味认知改变的结果。与野生型小鼠相比，GRPR基因敲除小鼠更喜欢其他小鼠的气味。在Brs3基因敲除的小鼠中，我们发现轻度肥胖伴高血压。对Brs3基因敲除小鼠的行为学检测显示，小鼠对可口和讨厌的味觉刺激都有高反应性。此外，Brs3基因敲除小鼠改变了对新的社会环境的反应。隔离饲养导致Brs3基因敲除小鼠体重增加和食物消耗增加。这些结果提示蛙皮素样肽受体系统在高级脑功能中起着重要作用。除了行为学检查，我们还试图分离Brs3的一个未知的内源配体，但我们没有在本研究中鉴定该配体。

In this study, we aimed to clarify the physiological role of bombesin-like peptide receptors in mammalian brain. Previous studies showed an involvement of the system in various biological aspects, however, individual role of each bombesin-like peptide receptor in the aspects remains elusive. We generated knockout mice of three mammalian bombesin-like peptide receptors which are gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR) and bombesin receptor subtype 3 (BRS3). Behavioral analyses of the knockout mice revealed that GRPR knockout mice showed increased social responses and social investigatory behaviors. Since treatment of tranquilizer did not change the responses in GRPR knockout, increased social activities in GRPR knockout mice was unlikely caused by altered anxiety. Rather, the behavior of the knockout mice was thought to be a consequence of altered cognition of odors. GRPR knockout mice preferred the odor of other mice to their own, in contrast to wild type mice. In BRS3 knockout mice, we found mild obesity with high blood pressure. Behavioral examination of BRS3 knockout mice revealed hyperresponsiveness to palatable and aversive taste stimuli. In addition, BRS3 knockout mice had altered responsiveness to novel and social environment. Isolation rearing caused increased gain of body weight and food consumption in BRS3 knockout mice. These results suggest that the bombesin-like peptide receptor system is an important player in higher brain function. Besides the behavioral examination, we also tried to isolate a unknown endogenous ligand for BRS3, however, we did not identify the ligand in the term of this study.