National Institute of Biological Sciences, Beijing, 102206, China.
National Institute of Biological Sciences, Beijing, 102206, China; PTN Graduate Program, School of Life Sciences, Peking University, Beijing 100081, China.
Neuron. 2017 Jul 5;95(1):138-152.e5. doi: 10.1016/j.neuron.2017.05.031. Epub 2017 Jun 15.
Stress-induced hyperglycemia is a fundamental adaptive response that mobilizes energy stores in response to threats. Here, our examination of the contributions of the central catecholaminergic (CA) neuronal system to this adaptive response revealed that CA neurons in the ventrolateral medulla (VLM) control stress-induced hyperglycemia. Ablation of VLM CA neurons abolished the hyperglycemic response to both physical and psychological stress, whereas chemogenetic activation of these neurons was sufficient to induce hyperglycemia. We further found that CA neurons in the rostral VLM, but not those in the caudal VLM, cause hyperglycemia via descending projections to the spinal cord. Monosynaptic tracing experiments showed that VLM CA neurons receive direct inputs from multiple stress-responsive brain areas. Optogenetic studies identified an excitatory PVN-VLM circuit that induces hyperglycemia. This study establishes the central role of VLM CA neurons in stress-induced hyperglycemia and substantially expands our understanding of the central mechanism that controls glucose metabolism.
应激性高血糖是一种基本的适应性反应，它能调动能量储备以应对威胁。在这里，我们研究了中枢儿茶酚胺（CA）神经元系统对这种适应性反应的贡献，结果表明，腹外侧延髓（VLM）中的 CA 神经元控制应激性高血糖。VLM CA 神经元的消融消除了对身体和心理应激的高血糖反应，而这些神经元的化学遗传激活足以诱导高血糖。我们进一步发现，腹侧 VLM 的 CA 神经元，而不是尾侧 VLM 的 CA 神经元，通过向脊髓的下行投射引起高血糖。单突触追踪实验表明，VLM CA 神经元接收来自多个应激反应性脑区的直接输入。光遗传研究确定了一个诱导高血糖的兴奋性 PVN-VLM 回路。这项研究确立了 VLM CA 神经元在应激性高血糖中的核心作用，并大大扩展了我们对控制葡萄糖代谢的中枢机制的理解。
