Neuroscience Graduate Program, Charlottesville, Virginia, USA.
Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
J Neurochem. 2018 Apr;145(1):6-18. doi: 10.1111/jnc.14315. Epub 2018 Mar 25.
Myelin, an insulating membrane that enables rapid action potential propagation, is an essential component of an efficient, functional vertebrate nervous system. Oligodendrocytes, the myelinating glia of the central nervous system (CNS), produce myelin throughout the CNS, which requires continuous proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Because myelination is essential for efficient neurotransmission, researchers hypothesize that neuronal signals may regulate the cascade of events necessary for this process. The ability of oligodendrocytes and oligodendrocyte progenitor cells to detect and respond to neuronal activity is becoming increasingly appreciated, although the specific signals involved are still a matter of debate. Recent evidence from multiple studies points to purinergic signaling as a potential regulator of oligodendrocyte development and differentiation. Adenosine triphosphate (ATP) and its derivatives are potent signaling ligands with receptors expressed on many populations of cells in the nervous system, including cells of the oligodendrocyte lineage. Release of ATP into the extracellular space can initiate a multitude of signaling events, and these downstream signals are specific to the particular purinergic receptor (or receptors) expressed, and whether enzymes are present to hydrolyze ATP to its derivatives adenosine diphosphate and adenosine, each of which can activate their own unique downstream signaling cascades. This review will introduce purinergic signaling in the CNS and discuss evidence for its effects on oligodendrocyte proliferation, differentiation, and myelination. We will review sources of extracellular purines in the nervous system and how changes in purinergic receptor expression may be coupled to oligodendrocyte differentiation. We will also briefly discuss purinergic signaling in injury and diseases of the CNS.
髓鞘是一种绝缘膜，使动作电位快速传播，是高效、功能正常的脊椎动物神经系统的重要组成部分。少突胶质细胞是中枢神经系统（CNS）的髓鞘形成胶质细胞，在整个 CNS 中产生髓鞘，这需要少突胶质前体细胞的持续增殖、迁移和分化。由于髓鞘对于有效的神经传递至关重要，研究人员假设神经元信号可能调节这一过程所需的级联事件。少突胶质细胞和少突胶质前体细胞检测和响应神经元活动的能力正越来越受到重视，尽管涉及的具体信号仍存在争议。来自多项研究的最新证据表明，嘌呤能信号是调节少突胶质细胞发育和分化的潜在调节剂。三磷酸腺苷（ATP）及其衍生物是具有潜力的信号配体，在神经系统的许多细胞群体中表达有受体，包括少突胶质细胞谱系的细胞。ATP 释放到细胞外空间可以引发多种信号事件，这些下游信号取决于表达的特定嘌呤能受体（或受体），以及是否存在将 ATP 水解为其衍生物二磷酸腺苷和腺苷的酶，每种衍生物都可以激活自己独特的下游信号级联反应。这篇综述将介绍中枢神经系统中的嘌呤能信号，并讨论其对少突胶质细胞增殖、分化和髓鞘形成的影响。我们将回顾神经系统中细胞外嘌呤的来源，以及嘌呤能受体表达的变化如何与少突胶质细胞分化相关联。我们还将简要讨论中枢神经系统损伤和疾病中的嘌呤能信号。
