Center for Neurosciences, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
Medical School, Research Group for Mood Disorders, Department of Anatomy and Centre for Neuroscience, University of Pécs, Szigeti út 12, 7624, Pécs, Hungary.
Neurochem Res. 2024 Dec;49(12):3277-3296. doi: 10.1007/s11064-024-04238-1. Epub 2024 Sep 12.
The Edinger-Westphal nucleus (EW) is a midbrain nucleus composed of a preganglionic, cholinergic subpopulation and a densely clustered peptidergic subpopulation (EWcp). The EWcp is one of the few brain regions that show consistent induction of FOS following voluntary alcohol intake. Previous results in rodents point to urocortin 1 (UCN1) as one of the peptides most involved in the control of ethanol intake and preference. Notably, the functions described for UCN1, such as reward processing, stress coping or the regulation of feeding behavior are similar to those described for the neuropeptide neuromedin U (NMU). Interestingly, NMU has been recently associated with the modulation of alcohol-related behaviors. However, little is known about the expression and functionality of NMU neurons in alcohol-responsive areas. In this study, we used the recently developed Nmu-Cre knock-in mouse model to examine the expression of NMU in the subaqueductal paramedian zone comprising the EWcp. We delved into the characterization and co-expression of NMU with other markers already described in the EWcp. Moreover, using FOS as a marker of neuronal activity, we tested whether NMU neurons were sensitive to acute alcohol administration. Overall, we provided novel insights on NMU expression and functionality in the EW region. We showed the presence of NMU within a subpopulation of UCN1 neurons in the EWcp and demonstrated that this partial co-expression does not interfere with the responsivity of UCN1-containing cells to alcohol. Moreover, we proposed that the UCN1 content in these neurons may be influenced by sex.
脑桥导水管周围灰质正中核（Edinger-Westphal nucleus，EW）是由节前胆碱能亚群和肽能密集簇亚群（EWcp）组成的中脑核团。EWcp 是少数几个在自愿摄入酒精后能持续诱导 FOS 表达的脑区之一。啮齿动物的先前研究结果表明，孤啡肽 1（urocortin 1，UCN1）是参与控制乙醇摄入和偏好的肽类之一。值得注意的是，UCN1 的功能，如奖励处理、应激应对或进食行为调节，与神经肽神经调节素 U（neuropeptide neuromedin U，NMU）的功能相似。有趣的是，NMU 最近与调节与酒精相关的行为有关。然而，关于在酒精反应性区域中 NMU 神经元的表达和功能知之甚少。在这项研究中，我们使用最近开发的 Nmu-Cre 敲入小鼠模型来研究包含在 EWcp 中的脑桥导水管周围正中区亚区中 NMU 的表达。我们深入研究了 NMU 在 EWcp 中与其他已描述标志物的特征和共表达。此外，我们使用 FOS 作为神经元活性的标志物，测试了 NMU 神经元是否对急性酒精处理敏感。总的来说，我们提供了关于 NMU 在 EW 区域的表达和功能的新见解。我们发现 NMU 存在于 EWcp 中的 UCN1 神经元亚群中，并证明这种部分共表达不会干扰 UCN1 细胞对酒精的反应性。此外，我们提出这些神经元中 UCN1 的含量可能受性别影响。
