Edinburgh Research Explorer Developmental expression of orphan g protein-coupled receptor 50 in the mouse brain

: Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identi fi ed as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a speci fi c function has not been identi fi ed. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identi fi ed novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis.

精神障碍具有复杂的病因，是由多种遗传风险因素和应激性生活事件之间的相互作用导致的。孤儿G蛋白偶联受体50（GPR50）已被确定为女性双相情感障碍和重度抑郁症的遗传风险因素，并且还有其他遗传和功能证据将GPR50与神经突生长、脂质代谢以及适应性产热和蛰伏联系起来。然而，在缺乏配体的情况下，其特定功能尚未确定。先前已有报道称成年GPR50在控制下丘脑 - 垂体 - 肾上腺（HPA）轴的脑区表达，但其发育过程中的表达情况未知。在本研究中，我们利用逆转录聚合酶链反应（rt - PCR）和免疫组织化学技术对发育中和成年小鼠大脑中的GPR50以及三种蛋白质相互作用因子进行了广泛的表达分析。Gpr50在胚胎第13天（E13）表达，在E18达到峰值，且主要由神经元表达。此外，我们还确定了Gpr50表达的新区域，包括参与神经递质信号传导的脑干核团：蓝斑、黑质和中缝核，以及参与代谢稳态的核团。在E18和成年期，Gpr50与酵母双杂交相互作用因子Nogo - A、Abca2和Cdh8在下丘脑、杏仁核、皮质以及选定的脑干核中共定位。通过这项研究，我们确定了GPR50与神经递质信号传导之间的联系，并强化了其在应激反应和能量稳态中可能发挥的作用。