Department of Physiology and Neurobiology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
Glia. 2010 Nov 15;58(15):1775-81. doi: 10.1002/glia.21057.
Nitric oxide (NO) has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission, but its cellular source has remained unresolved as the neuronal isoform of NO synthase (nNOS) in many brain regions is expressed only by small subsets of inhibitory neurons. It is generally believed that the glial NO-producing isoform (iNOS) is not expressed in the normal brain, but rather it undergoes a transcription-mediated up-regulation following an immunological challenge. Therefore, the involvement of iNOS in modulating normal neuronal functions has been largely ignored. Here I review evidence to the contrary: I summarize data pointing to the existence of a functioning iNOS in normal undisturbed mammalian brains, and experimental results tracing this expression to astrocytes. Finally, I review recent findings asserting that iNOS-dependent NO modulates synaptic release from presynaptic terminals. Based on these data, I propose that astrocytes express basal levels of iNOS. Flanking synaptic elements, astrocytes are perfectly positioned to release NO and affect synaptic transmission.
一氧化氮（NO）长期以来一直被认为是一种非典型的神经元信使，影响兴奋性突触传递，但由于许多脑区的神经元型一氧化氮合酶（nNOS）仅由一小部分抑制性神经元表达，其细胞来源仍未得到解决。一般认为，胶质细胞产生的一氧化氮同工酶（iNOS）在正常脑中不表达，而是在免疫挑战后通过转录介导的上调表达。因此，iNOS 参与调节正常神经元功能在很大程度上被忽视了。在这里，我回顾了相反的证据：我总结了指向正常未受干扰的哺乳动物大脑中存在功能正常的 iNOS 的数据，并追踪到这种表达存在于星形胶质细胞中的实验结果。最后，我回顾了最近的发现，断言 iNOS 依赖性的 NO 调节来自突触前末梢的突触释放。基于这些数据，我提出星形胶质细胞表达基础水平的 iNOS。位于突触旁的星形胶质细胞可以释放 NO 并影响突触传递。
