Properties of primary cilia in melanin-concentrating hormone receptor 1-bearing hippocampal neurons in vivo and in vitro

• Published in: Neurochemistry international 2021-01, Vol.142, p.104902-104902, Article 104902
• Main Authors: Kobayashi, Yuki, Okada, Tomoya, Miki, Daisuke, Sekino, Yuko, Koganezawa, Noriko, Shirao, Tomoaki, Diniz, Giovanne B., Saito, Yumiko
• Format: Article
• Language: English
• Subjects: Cilia length; Fasting; Hippocampus; Melanin-concentrating hormone; Melanin-concentrating hormone receptor 1; Primary cilia
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2020.104902

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. •MCH induces ciliary shortening via neuronal ciliary MCHR1 in hippocampal neurons.•MCH has similar effects on cilia in the CA1 region of hippocampal slice cultures.•Gi/o and Akt mediates cilia shortening in MCHR1-expressing hippocampal neurons.•Hippocampal cilia lengths in the CA1 region are reduced in mice fasted for 48 h.