Neuropeptide S Induces Acute Anxiolysis by Phospholipase C-Dependent Signaling within the Medial Amygdala
Neuropeptide S Induces Acute Anxiolysis by Phospholipase C-Dependent Signaling within the Medial Amygdala
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DOI：
10.1038/npp.2017.169
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发表时间：
2018-04-01
影响因子：
7.6
通讯作者：
Neumann, Inga D.
中科院分区：
文献类型：
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作者：
Grund, Thomas;Neumann, Inga D.
神经肽S（NPS）是大脑重要的抗焦虑物质。然而，NPS 受体 (NPSR) 激活下游的信号通路（NPS 行为效应的基础）仍然很大程度上未知。在这里，我们表明，将 NPS（0.2 nmol/0.5 μl）双侧微量输注到雄性成年 Wistar 大鼠的内侧杏仁核（MeA）中，可以减少高架十字迷宫和开放视野中的焦虑相关行为。此外，如杏仁核组织微穿孔脑室内注射NPS（1nmol/5μl）所示（1）诱发CaMKII的磷酸化和合成。与代表 Ca2+ 流入的参考蛋白 β-微管蛋白相关，(2) 诱导丝裂原激活蛋白激酶 ERK1/2 的磷酸化。通过在 MeA 中使用 U73122 (0.5 nmol/0.5 μl) 局部抑制磷脂酶 C 信号传导，可以阻止 NPS 诱导的抗焦虑作用，表明该途径的行为相关性。相反，使用2',5'-二脱氧腺苷(12.5 nmol/0.5 μl)对腺苷酸环化酶信号传导进行局部药理阻断未能抑制注入MeA的NPS的抗焦虑作用。因此，NPS 依赖于 NPSR 介导的磷脂酶 C 信号传导，促进 MeA 内的急性抗焦虑作用。总而言之，我们的研究扩展了有关 NPS 强效抗焦虑作用的细胞内信号传导机制的知识。
Neuropeptide S (NPS) is an important anxiolytic substance of the brain. However, the signaling pathways downstream of NPS receptor (NPSR) activation, underlying the behavioral effect of NPS, remain largely unknown. Here, we show that bilateral microinfusion of NPS (0.2 nmol/0.5 mu l) into the medial amygdala (MeA) of male adult Wistar rats reduced anxiety-related behavior on both the elevated plus-maze and the open field. Moreover, as shown in amygdala tissue micropunches intracerebroventricular infusion of NPS (1 nmol/5 mu l) (1) evoked phosphorylation and synthesis of CaMKII. in relation to reference protein beta-tubulin representing Ca2+ influx, and (2) induced phosphorylation of mitogen-activated protein kinase ERK1/2. The NPS-induced anxiolysis was prevented by local inhibition of phospholipase C signaling using U73122 (0.5 nmol/0.5 mu l) in the MeA, indicating the behavioral relevance of this pathway. Conversely, local pharmacological blockade of adenylyl cyclase signaling using 2', 5'-dideoxyadenosine (12.5 nmol/0.5 mu l) failed to inhibit the anxiolytic effect of NPS infused into the MeA. Hence, NPS promotes acute anxiolysis within the MeA dependent on NPSR-mediated phospholipase C signaling. Taken together, our study extends the knowledge about the intracellular signaling mechanisms underlying the potent anxiolytic profile of NPS.