Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany.
Purinergic Signal. 2012 Sep;8(3):629-57. doi: 10.1007/s11302-012-9300-0. Epub 2012 May 1.
Astrocytes are fundamental for central nervous system (CNS) physiology and are the fulcrum of neurological diseases. Astroglial cells control development of the nervous system, regulate synaptogenesis, maturation, maintenance and plasticity of synapses and are central for nervous system homeostasis. Astroglial reactions determine progression and outcome of many neuropathologies and are critical for regeneration and remodelling of neural circuits following trauma, stroke, ischaemia or neurodegenerative disorders. They secrete multiple neurotransmitters and neurohormones to communicate with neurones, microglia and the vascular walls of capillaries. Signalling through release of ATP is the most widespread mean of communication between astrocytes and other types of neural cells. ATP serves as a fast excitatory neurotransmitter and has pronounced long-term (trophic) roles in cell proliferation, growth, and development. During pathology, ATP is released from damaged cells and acts both as a cytotoxic factor and a proinflammatory mediator, being a universal "danger" signal. In this review, we summarise contemporary knowledge on the role of purinergic receptors (P2Rs) in a variety of diseases in relation to changes of astrocytic functions and nucleotide signalling. We have focussed on the role of the ionotropic P2X and metabotropic P2YRs working alone or in concert to modify the release of neurotransmitters, to activate signalling cascades and to change the expression levels of ion channels and protein kinases. All these effects are of great importance for the initiation, progression and maintenance of astrogliosis-the conserved and ubiquitous glial defensive reaction to CNS pathologies. We highlighted specific aspects of reactive astrogliosis, especially with respect to the involvement of the P2X(7) and P2Y(1)R subtypes. Reactive astrogliosis exerts both beneficial and detrimental effects in a context-specific manner determined by distinct molecular signalling cascades. Understanding the role of purinergic signalling in astrocytes is critical to identifying new therapeutic principles to treat acute and chronic neurological diseases.
星形胶质细胞是中枢神经系统 (CNS) 生理学的基础，也是神经疾病的支点。星形胶质细胞控制神经系统的发育，调节突触的发生、成熟、维持和可塑性，是神经系统内稳态的核心。星形胶质细胞反应决定了许多神经病理学的进展和结果，对于创伤、中风、缺血或神经退行性疾病后神经回路的再生和重塑至关重要。它们分泌多种神经递质和神经激素与神经元、小胶质细胞和毛细血管的血管壁进行通讯。通过释放 ATP 进行信号传递是星形胶质细胞与其他类型神经细胞之间最广泛的通讯方式。ATP 作为一种快速兴奋性神经递质，在细胞增殖、生长和发育中具有显著的长期（营养）作用。在病理状态下，ATP 从受损细胞中释放出来，既作为细胞毒性因子，又作为促炎介质，是一种通用的“危险”信号。在这篇综述中，我们总结了嘌呤能受体 (P2R) 在与星形胶质细胞功能和核苷酸信号变化相关的各种疾病中的作用的当代知识。我们重点介绍了离子型 P2X 和代谢型 P2YR 的作用，它们单独或协同作用，改变神经递质的释放，激活信号级联，并改变离子通道和蛋白激酶的表达水平。所有这些效应对于星形胶质细胞反应的启动、进展和维持都非常重要，这是一种对 CNS 病理的保守且普遍的胶质防御反应。我们强调了反应性星形胶质细胞的特定方面，特别是涉及 P2X(7) 和 P2Y(1)R 亚型的方面。反应性星形胶质细胞以特定分子信号级联决定的特定方式发挥有益和有害作用。了解嘌呤能信号在星形胶质细胞中的作用对于确定治疗急性和慢性神经疾病的新治疗原则至关重要。
