近日，奥地利维也纳医科大学教授Tibor Harkany及其研究组提出，脑干-下丘脑神经元回路在高温下减少进食。相关论文发表在2024年3月27日出版的《自然》杂志上。

该课题组人员表明伸长细胞在急性热刺激下被激活，并且在之后减少食物摄入是必要的。病毒介导的基因操作和环路图谱表明，臂旁核的温度感觉谷氨酸能神经元直接或通过下丘脑二级神经元支配伸长细胞。伸长细胞中热依赖性Fos的表达表明它们有能力产生信号分子，包括血管内皮生长因子A (VEGFA)。与将VEGFA排入脑脊液产生全身效应不同，VEGFA是沿着弓形核细胞的实质释放的。

VEGFA增加了Flt1表达多巴胺和agouti相关肽(Agrp)的神经元的峰值阈值，它们启动厌食信号输出。事实上，在热中性状态下，急性高温和谷氨酸能臂旁神经元的化学发生激活都会减少食物摄入数小时，这在某种程度上对Vegfa功能丧失和囊泡相关膜蛋白2 (VAMP2)依赖性胞外分泌的阻断都很敏感。总的来说，他们定义了一个多模态神经回路，其中伸长细胞将臂旁感觉与代谢密码的长期执行联系起来。

据介绍，经验证据表明，热暴露会减少食物摄入量。然而，尽管桥脑臂旁核中的初级热感神经元已经得到了很好的表征，但在感觉和代谢模式之间形成相关连接的神经回路结构和信号机制仍然未知。伸长细胞是沿第三脑室壁的一种特化细胞，在脑实质和脑室系统之间双向运输激素和信号分子。

附：英文原文

Title: A brainstem–hypothalamus neuronal circuit reduces feeding upon heat exposure

Author: Benevento, Marco, Alpr, Aln, Gundacker, Anna, Afjehi, Leila, Balueva, Kira, Hevesi, Zsofia, Hanics, Jnos, Rehman, Sabah, Pollak, Daniela D., Lubec, Gert, Wulff, Peer, Prevot, Vincent, Horvath, Tamas L., Harkany, Tibor

Issue&Volume: 2024-03-27

Abstract: Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain’s parenchyma and ventricular system3,4,5,6,7,8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.

DOI: 10.1038/s41586-024-07232-3

Source: https://www.nature.com/articles/s41586-024-07232-3