Thorsell Annika, Mathé Aleksander A
Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Front Endocrinol (Lausanne). 2017 Jul 31;8:178. doi: 10.3389/fendo.2017.00178. eCollection 2017.
Neuropeptide Y (NPY), a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS), as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide's regulation of disease states, suggest that modulation of the activity of the NPY system receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, ligands aimed at different receptor subtypes, may be attractive targets for treatment development for affective disorders, as well as for alcohol use disorders.
神经肽Y（NPY）是一种在进化过程中高度保守的神经肽，在中枢神经系统（CNS）以及肠道和心血管系统等外周组织中含量很高。该肽通过多种受体亚型发挥作用，所有这些亚型都属于G蛋白偶联受体超家族。在这些亚型中，Y1和Y2研究得最为透彻，其次是Y5亚型。NPY及其受体已被证明在例如情感障碍、药物/酒精使用障碍和能量稳态等潜在事件的中枢调节中具有重要作用。此外，在中枢神经系统内，NPY还影响睡眠调节和昼夜节律、记忆功能、组织生长和可塑性。NPY在情绪和焦虑障碍以及酒精使用障碍的病因学和病理生理学中的潜在作用已得到广泛研究。这种关注是由早期关于NPY参与应激急性反应的迹象引发的，后来还有数据表明在慢性或反复暴露于不良事件期间NPY在中枢神经系统内的改变中起作用。NPY的这些功能，除了该肽对疾病状态的调节外，表明调节NPY系统的活性（通过受体激动剂/拮抗剂）可能是情感障碍以及酒精使用障碍的一种推定治疗机制。在本综述中，我们概述了关于NPY系统与焦虑和应激（急性以及慢性）相关的研究结果；此外，我们讨论创伤后应激障碍以及部分抑郁症。此外，我们总结了酒精使用障碍和相关行为的研究结果。最后，我们简要提及可能对NPY功能和调节很重要的遗传以及表观遗传机制。总之，我们建议通过针对不同受体亚型的配体调节中枢神经系统内的NPY能活性，可能是情感障碍以及酒精使用障碍治疗开发的有吸引力的靶点。
