The primary cilium is a solitary organelle that organizes a sensitive signaling hub in a highly ordered microenvironment. Cilia are plastic structures, changing their length in response to bioactive substances, and ciliary length may be regulated to ensure efficient signaling capacity. Mammalian brain neurons possess primary cilia that are enriched in a set of G protein-coupled receptors (GPCRs), including the feeding-related melanin-concentrating hormone (MCH) receptor 1 (MCHR1). We previously demonstrated a novel biological phenomenon, ciliary MCHR1-mediated cilia length shortening through Gi/o and Akt signaling, using a simple cell culture model of human retinal pigmented epithelial RPE1 cells exogenously expressing MCHR1. In the present study, we characterized the properties of endogenous MCHR1-expressing primary cilia in hippocampal neurons in rodents. Using cultured dissociated rat hippocampal neurons in vitro, we showed that MCH triggered cilia length reduction involved in MCHR1-Gi/o and -Akt signaling. In rat hippocampal slice cultures with preservation of the cytoarchitecture and cell populations, ciliary MCHR1 was abundantly located in the CA1 and CA3 regions, but not in the dentate gyrus. Notably, treatment of slice cultures with MCH induced Gi/o- and Akt-dependent cilia shortening in the CA1 region without influencing cilia length in the CA3 region. Regarding the in vivo mouse brain, we observed higher levels of ciliary MCHR1 in the CA1 and CA3 regions as well as in slice cultures. In the starved state mice, a marked increase in MCH mRNA expression was detected in the lateral hypothalamus. Furthermore, MCHR1-positive cilia length in the hippocampal CA1 region was significantly shortened in fasted mice compared with fed mice. The present findings focused on the hippocampus provide a potential approach to investigate how MCHR1-driven cilia shortening regulates neuronal activity and physiological function toward feeding and memory tasks.

初级纤毛是一种单独的细胞器，在高度有序的微环境中组织一个敏感的信号中心。纤毛是塑料结构，可根据生物活性物质改变其长度，并且可以调节纤毛长度以确保有效的信号传递能力。哺乳动物脑神经元拥有富含一组 G 蛋白偶联受体 (GPCR) 的初级纤毛，包括与进食相关的黑色素浓缩激素 (MCH) 受体 1 (MCHR1)。我们之前使用外源表达 MCHR1 的人视网膜色素上皮 RPE1 细胞的简单细胞培养模型，证明了一种新的生物学现象，即纤毛 MCHR1 介导的纤毛长度通过 Gi/o 和 Akt 信号缩短。在目前的研究中，我们表征了啮齿动物海马神经元中表达内源性 MCHR1 的初级纤毛的特性。使用培养的分离的大鼠海马神经元在体外，我们发现 MCH 触发纤毛长度减少，涉及 MCHR1-Gi/o 和 -Akt 信号传导。在保留细胞结构和细胞群的大鼠海马切片培养物中，纤毛 MCHR1 大量位于 CA1 和 CA3 区域，但不在齿状回中。值得注意的是，用 MCH 处理切片培养物在 CA1 区域诱导 Gi/o 和 Akt 依赖性纤毛缩短，而不影响 CA3 区域的纤毛长度。关于体内在小鼠大脑中，我们在 CA1 和 CA3 区域以及切片培养物中观察到更高水平的睫状体 MCHR1。在饥饿状态的小鼠中，在外侧下丘脑中检测到 MCH mRNA 表达的显着增加。此外，与进食小鼠相比，禁食小鼠海马 CA1 区 MCHR1 阳性纤毛长度显着缩短。目前集中在海马体上的发现提供了一种潜在的方法来研究 MCHR1 驱动的纤毛缩短如何调节神经元活动和生理功能，以完成进食和记忆任务。