Women and Children's Medical Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Neurology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Behav Brain Funct. 2024 Jul 4;20(1):18. doi: 10.1186/s12993-024-00244-z.
Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated.
In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests.
We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects.
This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.
焦虑症是最常见的精神障碍之一。胃饥饿素是一种关键的食欲肽，它调节食物摄入和代谢。最近，胃饥饿素系统因其在包括抑郁和焦虑在内的精神疾病中的关键作用而引起了更多的关注。然而，其涉及的潜在神经机制尚未得到充分研究。
在本研究中，通过免疫荧光、qRT-PCR、神经药理学、分子操作和行为测试，研究了正常和急性应激大鼠伏隔核（NAc）核心中的胃饥饿素信号对焦虑样行为的影响及其潜在机制。
我们报告称，胃饥饿素注射到 NAc 核心会引起明显的抗焦虑作用。胃饥饿素受体生长激素促分泌素受体（GHSR）高度定位于 NAc 核心神经元并表达于此。GHSR 拮抗剂阻断了胃饥饿素引起的抗焦虑作用。此外，GHSR 的分子敲低会引起焦虑样效应。此外，胃饥饿素注射或 GHSR 在 NAc 核心中的过表达可减轻急性束缚应激引起的焦虑样效应。
这项研究表明，NAc 核心中的胃饥饿素及其受体 GHSR 积极参与调节急性应激引起的焦虑，为通过靶向胃饥饿素信号系统治疗焦虑症提供了机会。
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