Wei Catherine J, Li Wei, Chen Jiang-Fan
Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
Biochim Biophys Acta. 2011 May;1808(5):1358-79. doi: 10.1016/j.bbamem.2010.12.018. Epub 2010 Dec 23.
Endogenous adenosine is a widely distributed upstream regulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways that converge to contribute to the expression of an array of important brain functions. Over the past decade, the generation and characterization of genetic knockout models for all four G-protein coupled adenosine receptors, the A1 and A2A receptors in particular, has confirmed and extended the neuromodulatory and integrated role of adenosine receptors in the control of a broad spectrum of normal and abnormal brain functions. After a brief introduction of the available adenosine receptor knockout models, this review focuses on findings from the genetic knockout approach, placing particular emphasis on the most recent findings. This review is organized into two sections to separately address (i) the role of adenosine receptors in normal brain processes including neuroplasticity, sleep-wake cycle, motor function, cognition, and emotion-related behaviors; and (ii) their role in the response to various pathologic insults to brain such as ischemic stroke, neurodegeneration, or brain dysfunction/disorders. We largely limit our overview to the prominent adenosine receptor subtypes in brain-the A1 and A2A receptors-for which numerous genetic knockout studies on brain function are available. A1 and A2A receptor knockouts have provided significant new insights into adenosine's control of complex physiologic (e.g., cognition) and pathologic (e.g., neuroinflammation) phenomena. These findings extend and strengthen the support for A1 and A2A receptors in brain as therapeutic targets in several neurologic and psychiatric diseases. However, they also emphasize the importance of considering the disease context-dependent effect when developing adenosine receptor-based therapeutic strategies.
内源性腺苷是一种广泛分布的上游调节剂，作用于多种神经递质、受体和信号通路，这些共同作用有助于一系列重要脑功能的表达。在过去十年中，针对所有四种G蛋白偶联腺苷受体，特别是A1和A2A受体的基因敲除模型的构建和特性研究，证实并扩展了腺苷受体在控制广泛的正常和异常脑功能中的神经调节和整合作用。在简要介绍现有的腺苷受体敲除模型后，本综述重点关注基因敲除方法的研究结果，特别强调最新发现。本综述分为两个部分，分别阐述（i）腺苷受体在正常脑过程中的作用，包括神经可塑性、睡眠-觉醒周期、运动功能、认知以及与情绪相关的行为；（ii）它们在应对各种脑部病理损伤，如缺血性中风、神经退行性变或脑功能障碍/疾病时的作用。我们主要将概述局限于脑中突出的腺苷受体亚型——A1和A2A受体，针对它们有大量关于脑功能的基因敲除研究。A1和A2A受体敲除为腺苷对复杂生理（如认知）和病理（如神经炎症）现象的控制提供了重要的新见解。这些发现扩展并加强了将脑中的A1和A2A受体作为几种神经和精神疾病治疗靶点的依据。然而，它们也强调了在制定基于腺苷受体的治疗策略时考虑疾病背景依赖性效应的重要性。
