Saxon D W, Beitz A J
Department of Veterinary Pathobiology, University of Minnesota, St Paul 55108, USA.
Neuroscience. 1996 May;72(1):157-65. doi: 10.1016/0306-4522(95)00487-4.
Nitric oxide synthase and its product nitric oxide are believed to be significantly involved in neuronal degeneration associated with various excitotoxic events and in some acute and chronic neuropathological disease states. The synchronous activation of inferior olive neurons by the drug harmaline is known to produce tremorogenic activity in rats via increased stimulation of the olivocerebellar system. Following subcutaneous or intraperitoneal injection (15, 30 or 60 mg/kg) of harmaline and survival intervals of three days or more, NADPH-diaphorase histochemistry and nitric oxide synthase immunocytochemistry revealed nitric oxide synthase induction in Purkinje cells of the cerebellar vermis and paravermis, but not the lateral hemispheres. Double labeling with NADPH-diaphorase and calbindin revealed that induced Purkinje cells contain calbindin and that induced Purkinje cells are not necessarily associated with regions of Purkinje cell degeneration. The induction of nitric oxide synthase in a subpopulation of Purkinje cells may reflect a protective response of selected Purkinje cells to overstimulation of specific olivocerebellar projections. This is the first experimental model for the non-invasive induction of nitric oxide synthase in central nervous system neurons and as such may provide a useful tool for studying the induction of nitric oxide synthase associated with excitotoxic events.
一氧化氮合酶及其产物一氧化氮被认为与各种兴奋性毒性事件相关的神经元变性以及某些急性和慢性神经病理疾病状态密切相关。已知药物哈马灵对下橄榄核神经元的同步激活会通过增强对橄榄小脑系统的刺激在大鼠中产生震颤活性。在皮下或腹腔注射（15、30或60mg/kg）哈马灵并存活三天或更长时间后，NADPH-黄递酶组织化学和一氧化氮合酶免疫细胞化学显示，小脑蚓部和旁蚓部的浦肯野细胞中有一氧化氮合酶诱导，但外侧半球没有。用NADPH-黄递酶和钙结合蛋白进行双重标记显示，诱导的浦肯野细胞含有钙结合蛋白，并且诱导的浦肯野细胞不一定与浦肯野细胞变性区域相关。浦肯野细胞亚群中一氧化氮合酶的诱导可能反映了特定浦肯野细胞对特定橄榄小脑投射过度刺激的保护反应。这是中枢神经系统神经元中一氧化氮合酶非侵入性诱导的第一个实验模型，因此可能为研究与兴奋性毒性事件相关的一氧化氮合酶诱导提供一个有用的工具。
