Canine cognitive dysfunction (CCD) is an age-related disorder similar to human Alzheimer's disease (AD) that occurs in elderly dogs. Nitrosative stress has been implicated as one of the causes leading to neurodegenerative diseases, particularly AD. Its involvement in the development of CCD has not been studied so far. In the present study, immunohistochemical staining detected all three isoforms of nitric oxide synthases (nNOS, eNOS, and iNOS) and 3-nitrotyrosine (3-NT) in brains from CCD-affected dogs and non-demented control dogs in all layers of the canine frontal cortex. In CCD-affected and non-demented brains, nNOS was highly expressed in pyramidal-like neurons in the upper cortical layers. nNOS has also been observed in astrocytes in the CCD frontal cortex. The nNOS immunohistochemical staining was statistically significantly elevated in dogs with CCD in comparison to non-demented dogs. Blood vessel wall cells were positive for eNOS, which was also expressed in astrocytes and neurons. Intense 3-NT immunoreactivity was observed in the upper cortical layers, where amyloid-beta deposits spread in the last stage of CCD. Brain cells in the same area were highly immunoreactive for iNOS. This infers that neuroinflammation and nitrosative stress might exacerbate the neurodegenerative process in CCD-affected brains, ultimately leading to cognitive impairment.

犬认知功能障碍（CCD）是一种与年龄相关的疾病，类似于在老年犬中发生的人类阿尔茨海默氏病（AD）。亚硝酸盐应激被认为是导致神经退行性疾病，特别是AD的原因之一。迄今为止，尚未研究其在CCD开发中的参与。在本研究中，免疫组化染色检测了CCD感染犬和非痴呆对照犬大脑各层中一氧化氮合酶（nNOS，eNOS和iNOS）和3-硝基酪氨酸（3-NT）的所有三种同工型。犬额叶皮层。在受CCD影响和非痴呆的大脑中，nNOS在上皮层的锥体状神经元中高表达。在CCD额叶皮层的星形胶质细胞中也观察到了nNOS。与未痴呆的犬相比，CCD犬的nNOS免疫组织化学染色在统计学上显着升高。血管壁细胞对eNOS呈阳性，这也在星形胶质细胞和神经元中表达。在上皮层中观察到强烈的3-NT免疫反应性，其中淀粉样蛋白-β沉积物在CCD的最后阶段扩散。同一区域的脑细胞对iNOS具有高度免疫反应性。这表明神经炎症和亚硝化应激可能会加剧受CCD影响的大脑中的神经变性过程，最终导致认知障碍。β-淀粉样蛋白沉积物在CCD的最后阶段扩散。同一区域的脑细胞对iNOS具有高度免疫反应性。这表明神经炎症和亚硝化应激可能会加剧受CCD影响的大脑中的神经变性过程，最终导致认知障碍。β-淀粉样蛋白沉积物在CCD的最后阶段扩散。同一区域的脑细胞对iNOS具有高度免疫反应性。这表明神经炎症和亚硝化应激可能会加剧受CCD影响的大脑中的神经变性过程，最终导致认知障碍。