Activation of PPG neurons following acute stressors differentially involves hindbrain serotonin in male rats.
Activation of PPG neurons following acute stressors differentially involves hindbrain serotonin in male rats.
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DOI：
10.1016/j.neuropharm.2021.108477
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发表时间：
2021-04-01
影响因子：
4.7
通讯作者：
Hayes MR
中科院分区：
文献类型：
--
作者：
Leon RM;Borner T;Stein LM;Urrutia NA;De Jonghe BC;Schmidt HD;Hayes MR
在后脑内，5-羟色胺（5-HT）作为中枢胰高血糖素样肽-1（GLP-1）系统的调节剂发挥作用。5-HT和GLP-1之间的这种相互作用通过5-HT 2C和5-HT 3受体实现，并且与GLP-1介导的摄食行为相关。中枢GLP-1系统被各种应激源激活，激活下丘脑垂体肾上腺皮质（HPA）轴，并促成应激相关行为。5-HT是否调节GLP-1在应激反应中的作用尚不清楚。我们假设GLP-1产生神经元的多巴胺能调节（即，PPG神经元）是刺激特异性的，应激诱导的PPG活性是5-HT发挥作用的方式之一。在这项研究中，我们研究了5-HT 2C和5-HT 3受体介导的PPG神经元的激活孤束核（NTS）暴露于三种不同的急性应激：氯化锂（LiCl），可卡因（Coc），和新的束缚应激（RES）后的作用。结果表明，增加c-Fos表达PPG神经元后，氯化锂和RES-而不是可口可乐-是依赖于后脑5-HT 2C和5-HT 3受体信号。此外，依赖于5-HT信号传导来激活PPG神经元的应激源（即，氯化锂和RES）增加中缝尾侧（CR）内表达5-HT的神经元中c-Fos的表达，特别是在中缝大肌（RMg）中。最后，我们发现，RMg神经元支配NTS PPG神经元，这些PPG神经元中的一些位于靠近5-HT轴突，这表明RMg 5-HT表达神经元是负责从事NTS PPG神经元的5-HT输入的来源。总之，这些发现确定了一个直接的RMg到NTS通路负责5-HT对中枢GLP-1系统的调节作用-特别是通过激活5-HT 2C和5-HT 3受体-在促进急性应激反应。
Within the hindbrain, serotonin (5-HT) functions as a modulator of the central glucagon-like peptide-1 (GLP-1) system. This interaction between 5-HT and GLP-1 is achieved via 5-HT2C and 5-HT3 receptors and is relevant for GLP-1-mediated feeding behavior. The central GLP-1 system is activated by various stressors, activates the hypothalamic pituitary adrenocortical (HPA) axis, and contributes to stress-related behaviors. Whether 5-HT modulates GLP-1’s role in the stress response in unknown. We hypothesized that the serotonergic modulation of GLP-1-producing neurons (i.e., PPG neurons) is stimuli-specific and that stressed-induced PPG activity is one of the modalities in which 5-HT plays a role. In this study, we investigated the roles of 5-HT2C and 5-HT3 receptors in mediating the activation of PPG neurons in the nucleus tractus solitarius (NTS) following exposure to three different acute stressors: lithium chloride (LiCl), noncontingent cocaine (Coc), and novel restraint stress (RES). Results showed that increased c-Fos expression in PPG neurons following LiCl and RES—but not Coc—is dependent on hindbrain 5-HT2C and 5-HT3 receptor signaling. Additionally, stressors that depend on 5-HT signaling to activate PPG neurons (i.e., LiCl and RES) increased c-Fos expression in 5-HT-expressing neurons within the caudal raphe (CR), specifically in the raphe magnus (RMg). Finally, we showed that RMg neurons innervate NTS PPG neurons and that some of these PPG neurons lie in close proximity to 5-HT axons, suggesting RMg 5-HT-expressing neurons are the source of 5-HT input responsible for engaging NTS PPG neurons. Together, these findings identify a direct RMg to NTS pathway responsible for the modulatory effect of 5-HT on the central GLP-1 system—specifically via activation of 5-HT2C and 5-HT3 receptors—in the facilitation of acute stress responses.
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影响因子：
5
作者：
Hayes MR;Schmidt HD
通讯作者：
Schmidt HD
影响因子：
3.4
作者：
Carr, Gregory V.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
7.6
作者：
Hare, Brendan D.;Beierle, Jacob A.;Falls, William A.
通讯作者：
Falls, William A.
DOI：
10.3109/10253890.2015.1013531
发表时间：
2015
期刊：
Stress (Amsterdam, Netherlands)
影响因子：
--
作者：
Bundzikova-Osacka J;Ghosal S;Packard BA;Ulrich-Lai YM;Herman JP
通讯作者：
Herman JP
影响因子：
7.7
作者：
Cabou, Cendrine;Campistron, Gerard;Burcelin, Remy
通讯作者：
Burcelin, Remy