PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：焦虑症是最常见的精神障碍之一。Ghrelin是调节食物摄取和代谢的关键的促食性脑肠肽。最近,ghrelin系统因其在精神疾病中的关键作用而受到更多关注，包括抑郁和焦虑.然而,所涉及的潜在神经机制尚未得到充分研究.
方法：在本研究中，研究了正常和急性应激大鼠伏隔核ghrelin信号传导对焦虑样行为的影响和潜在机制，通过使用免疫荧光，qRT-PCR,神经药理学,分子操纵和行为测试。
结果：我们报道，在NAc核心注射生长素释放肽可引起显著的抗焦虑作用。Ghrelin受体生长激素促分泌素受体（GHSR）在NAc核心神经元中高度定位和表达。GHSR的拮抗作用阻断了生长素释放肽诱导的抗焦虑作用。此外，GHSR诱导的抗焦虑作用的分子敲低。此外，在NAc核心中注射ghrelin或过度表达GHSR可降低急性束缚应激诱导的焦虑作用。
结论：这项研究表明，NAc核心中的ghrelin及其受体GHSR积极参与调节急性应激引起的焦虑，并通过靶向ghrelin信号系统提供治疗焦虑症的机会。
方法：在本研究中，研究了正常和急性应激大鼠伏隔核ghrelin信号传导对焦虑样行为的影响和潜在机制，通过使用免疫荧光，qRT-PCR,神经药理学,分子操纵和行为测试。
结果：我们报道，在NAc核心注射生长素释放肽可引起显著的抗焦虑作用。Ghrelin受体生长激素促分泌素受体（GHSR）在NAc核心神经元中高度定位和表达。GHSR的拮抗作用阻断了生长素释放肽诱导的抗焦虑作用。此外，GHSR诱导的抗焦虑作用的分子敲低。此外，在NAc核心中注射ghrelin或过度表达GHSR可降低急性束缚应激诱导的焦虑作用。
结论：这项研究表明，NAc核心中的ghrelin及其受体GHSR积极参与调节急性应激引起的焦虑，并通过靶向ghrelin信号系统提供治疗焦虑症的机会。
