Fritz Eva Maria, Singewald Nicolas, De Bundel Dimitri
Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, University of Innsbruck, Innsbruck, Austria.
Department of Pharmaceutical Sciences, Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
Front Synaptic Neurosci. 2020 Oct 27;12:594484. doi: 10.3389/fnsyn.2020.594484. eCollection 2020.
Ghrelin is a peptide hormone released by specialized X/A cells in the stomach and activated by acylation. Following its secretion, it binds to ghrelin receptors in the periphery to regulate energy balance, but it also acts on the central nervous system where it induces a potent orexigenic effect. Several types of stressors have been shown to stimulate ghrelin release in rodents, including nutritional stressors like food deprivation, but also physical and psychological stressors such as foot shocks, social defeat, forced immobilization or chronic unpredictable mild stress. The mechanism through which these stressors drive ghrelin release from the stomach lining remains unknown and, to date, the resulting consequences of ghrelin release for stress coping remain poorly understood. Indeed, ghrelin has been proposed to act as a stress hormone that reduces fear, anxiety- and depression-like behaviors in rodents but some studies suggest that ghrelin may - in contrast - promote such behaviors. In this review, we aim to provide a comprehensive overview of the literature on the role of the ghrelin system in stress coping. We discuss whether ghrelin release is more than a byproduct of disrupted energy homeostasis following stress exposure. Furthermore, we explore the notion that ghrelin receptor signaling in the brain may have effects independent of circulating ghrelin and in what way this might influence stress coping in rodents. Finally, we examine how the ghrelin system could be utilized as a therapeutic avenue in stress-related psychiatric disorders (with a focus on anxiety- and trauma-related disorders), for example to develop novel biomarkers for a better diagnosis or new interventions to tackle relapse or treatment resistance in patients.
胃饥饿素是一种由胃内特殊的X/A细胞释放并通过酰化作用激活的肽类激素。分泌后,它与外周的胃饥饿素受体结合以调节能量平衡,但它也作用于中枢神经系统,在那里诱导强烈的促食欲作用。已表明多种类型的应激源可刺激啮齿动物释放胃饥饿素,包括营养应激源如食物剥夺,还有身体和心理应激源,如足部电击、社会挫败、强迫固定或慢性不可预测轻度应激。这些应激源促使胃饥饿素从胃黏膜释放的机制尚不清楚,并且迄今为止,胃饥饿素释放对应激应对的最终后果仍知之甚少。实际上,有人提出胃饥饿素作为一种应激激素可减少啮齿动物的恐惧、焦虑和抑郁样行为,但一些研究表明,相反,胃饥饿素可能会促进此类行为。在本综述中,我们旨在全面概述关于胃饥饿素系统在应激应对中作用的文献。我们讨论胃饥饿素释放是否不仅仅是应激暴露后能量稳态破坏的副产品。此外,我们探讨大脑中胃饥饿素受体信号传导可能具有独立于循环胃饥饿素的作用这一观点,以及这可能以何种方式影响啮齿动物的应激应对。最后,我们研究胃饥饿素系统如何可作为应激相关精神障碍(重点是焦虑和创伤相关障碍)治疗途径加以利用,例如开发新的生物标志物以实现更好的诊断,或开发新的干预措施以应对患者的复发或治疗抵抗。