Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, Gothenburg, Sweden.
J Neuroendocrinol. 2019 Jun;31(6):e12722. doi: 10.1111/jne.12722. Epub 2019 May 23.
Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6Rα) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6Rα present in this nucleus.
涉及中枢杏仁核 (CeA) 的神经元回路作为调节代谢功能的重要中心而备受关注。作为皮质下食物动机回路的一部分，CeA 与食物动机和饥饿有关。我们之前已经表明，白细胞介素 (IL)-6 可以作为胰高血糖素样肽-1 (GLP-1) 受体 (R) 刺激在大脑中代谢作用的下游介质，尽管这些作用的部位在很大程度上尚不清楚。在本研究中，我们使用新生成和验证的 RedIL6 报告小鼠品系来研究 CeA 中是否存在 IL-6，以及该核中 IL-6 和 GLP-1 之间可能存在的相互作用。IL-6 存在于 CeA 中，主要存在于该结构的内侧和外侧部分的细胞中，大多数含有 IL-6 的细胞也共同表达 GLP-1R。三重染色显示 GLP-1 含有纤维与突触小体共染色，靠近或与含有 IL-6 的细胞重叠。GLP-1R 刺激增强了 IL-6 mRNA 水平。发现 IL-6 受体-α (IL-6Rα) 在很大程度上存在于神经元 CeA 细胞中。通过电生理学，我们确定 CeA 中具有神经元特性的细胞可以在体外被 IL-6 给药迅速刺激。此外，将 IL-6 微注射到 CeA 中可以在 overnight 禁食的大鼠体内略微减少食物摄入。总之，CeA 中含有 IL-6 的细胞表达 GLP-1R，靠近含有 GLP-1 的突触，并且对 GLP-1R 激动剂处理表现出增加的 IL-6 mRNA。反过来，IL-6 在 CeA 中发挥生物学作用，可能通过该核中存在的 IL-6Rα。
