Busnelli Marta, Chini Bice
CNR, Institute of Neuroscience, Via Vanvitelli 32, Milan, 20129, Italy.
Department of Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, Milan, 20129, Italy.
Curr Top Behav Neurosci. 2018;35:3-29. doi: 10.1007/7854_2017_6.
Oxytocin (OT), a hypothalamic neuropeptide involved in regulating the social behaviour of all vertebrates, has been proposed as a treatment for a number of neuropsychiatric disorders characterised by deficits in the social domain. Over the last few decades, advances focused on understanding the social effects of OT and its role in physiological conditions and brain diseases, but much less has been done to clarify the molecular cascade of events involved in mediating such effects and in particular the cellular and molecular pharmacology of OT and its target receptor (OTR) in neuronal and glial cells.The entity and persistence of OT activity in the brain is closely related to the expression and regulation of the OTR expressed on the cell surface, which transmits the signal intracellularly and permits OT to affect cell function. Understanding the various signalling mechanisms mediating OTR-induced cell responses is crucial to determine the different responses in different cells and brain regions, and the success of OT and OT-derived analogues in the treatment of neurodevelopmental and psychiatric diseases depends on how well we can control such responses. In this review, we will consider the most important aspects of OT/OTR signalling by focusing on the molecular events involved in OT binding and coupling, on the main signalling pathways activated by the OTR in neuronal cells and on intracellular and plasma membrane OTR trafficking, all of which contribute to the quantitative and qualitative features of OT responses in the brain.
催产素（OT）是一种参与调节所有脊椎动物社会行为的下丘脑神经肽，已被提议用于治疗多种以社交领域功能缺陷为特征的神经精神疾病。在过去几十年中，研究进展主要集中在理解OT的社会效应及其在生理状况和脑部疾病中的作用，但在阐明介导此类效应所涉及的分子事件级联，特别是OT及其靶受体（OTR）在神经元和神经胶质细胞中的细胞和分子药理学方面所做的工作要少得多。OT在大脑中的活性的实体和持续性与细胞表面表达的OTR的表达和调节密切相关，OTR将信号传递到细胞内并使OT能够影响细胞功能。了解介导OTR诱导的细胞反应的各种信号传导机制对于确定不同细胞和脑区的不同反应至关重要，OT及其衍生类似物在治疗神经发育和精神疾病方面的成功取决于我们对这种反应的控制程度。在这篇综述中，我们将通过关注OT结合和偶联所涉及的分子事件、神经元细胞中OTR激活的主要信号通路以及细胞内和质膜OTR运输等OT/OTR信号传导的最重要方面进行探讨，所有这些都有助于大脑中OT反应的定量和定性特征。
