Thorns V, Hansen L, Masliah E
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.
Exp Neurol. 1998 Mar;150(1):14-20. doi: 10.1006/exnr.1997.6751.
Nitric oxide is a multifunctional molecule that acts as messenger/modulator in synaptogenesis and potential neurotoxin and is synthesized by three isozymes of Nitric oxide synthase (NOS). The role of NOS in Alzheimer's disease (AD) is unclear. For example, neurons in the entorhinal cortex (EC) that are highly vulnerable to neurodegeneration in AD express low levels of NOS and while it has been suggested that the inducible form of NOS is upregulated in AD, it is still not clear if the constitutive expressed isozyme (nNOS) is involved in the process of neurodegeneration. In order to better understand the role of nNOS in the pathogenesis of AD, sections from the EC and hippocampus (HC) of AD and control cases were immunohistochemically analyzed by single- and double-immunolabeling using antibodies against nNOS and PHF-tau. Semiquantitative assessment of numbers of nNOS expressing neurons in different areas of the HC and EC showed a remarkable loss of nNOS expressing neurons in the entorhinal cortex layer II and--less severe--CA1 and CA3 of the hippocampus in patients with AD. In addition, double-immunolabeling studies revealed that nNOS is strongly associated with neurofibrillary tangles and plaques. These findings indicate that nNOS expressing neurons are highly susceptible to neurodegeneration and that nNOS might contribute to the pathogenesis of AD.
一氧化氮是一种多功能分子，在突触形成中作为信使/调节剂发挥作用，同时也是潜在的神经毒素，它由一氧化氮合酶（NOS）的三种同工酶合成。NOS在阿尔茨海默病（AD）中的作用尚不清楚。例如，在内嗅皮质（EC）中，那些在AD中极易发生神经退行性变的神经元表达低水平的NOS，虽然有人提出在AD中诱导型NOS上调，但组成型表达的同工酶（nNOS）是否参与神经退行性变过程仍不清楚。为了更好地理解nNOS在AD发病机制中的作用，利用抗nNOS和PHF-tau的抗体，通过单免疫标记和双免疫标记对AD患者和对照病例的EC和海马体（HC）切片进行免疫组织化学分析。对HC和EC不同区域中表达nNOS的神经元数量进行半定量评估，结果显示AD患者内嗅皮质第II层以及海马体CA1和CA3区（程度较轻）中表达nNOS的神经元显著减少。此外，双免疫标记研究表明nNOS与神经原纤维缠结和斑块密切相关。这些发现表明，表达nNOS的神经元极易发生神经退行性变，并且nNOS可能参与AD的发病机制。
