Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients
Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients
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DOI：
10.1111/j.1474-9728.2004.00083.x
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发表时间：
2004-02-01
期刊：
影响因子：
7.8
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Ghanbari, HA;Ghanbari, K;Perry, G
氧化异常先于阿尔茨海默病的临床和病理表现，并且是该疾病中报道的最早的病理变化。嗅觉通路和粘膜也显示与脑中阿尔茨海默病相关的病理特征。嗅觉神经元是独特的，因为它们可以经历神经发生并且能够容易地在细胞培养中维持。在这项研究中，我们研究了神经元细胞培养来自嗅粘膜的阿尔茨海默病和对照患者的氧化应激反应。脂质过氧化（羟基壬烯醛），N-羟-（羧甲基）赖氨酸（糖氧化和脂质过氧化）和氧化应激反应（血红素加氧酶-1）的水平进行了测定免疫细胞化学。我们发现，与对照组相比，阿尔茨海默病神经元中检测的所有氧化应激标志物水平均升高。有趣的是，在一个阿尔茨海默氏病的病例中，我们发现羟基壬烯醛加合物在培养的神经元中约20%的细胞质溶酶体样结构中积累，但在对照患者的神经元中没有。这些溶酶体样结构存在于阿尔茨海默病患者大脑中约100%的脆弱神经元中。这项研究表明，阿尔茨海默病中氧化失衡的表现延伸到培养的嗅觉神经元。人嗅神经元的原代培养将有助于了解阿尔茨海默病的氧化损伤机制，甚至可以用于开发治疗策略。
Oxidative abnormalities precede clinical and pathological manifestations of Alzheimer's disease and are the earliest pathological changes reported in the disease. The olfactory pathways and mucosa also display the pathological features associated with Alzheimer's disease in the brain. Olfactory neurons are unique because they can undergo neurogenesis and are able to be readily maintained in cell culture. In this study, we examined neuronal cell cultures derived from olfactory mucosa of Alzheimer's disease and control patients for oxidative stress responses. Levels of lipid peroxidation (hydroxynonenal), N-epsilon-(carboxymethyl)lysine (glycoxidative and lipid peroxidation), and oxidative stress response (heme oxygenase-1) were measured immunocytochemically. We found increased levels for all the oxidative stress markers examined in Alzheimer's disease neurons as compared to controls. Interestingly, in one case of Alzheimer's disease, we found hydroxynonenal adducts accumulated in cytoplasmic lysosome-like structures in about 20% of neurons cultured, but not in neurons from control patients. These lysosome-like structures are found in about 100% of the vulnerable neurons in brains of cases of Alzheimer's disease. This study suggests that manifestations of oxidative imbalance in Alzheimer's disease extend to cultured olfactory neurons. Primary culture of human olfactory neurons will be useful in understanding the mechanism of oxidative damage in Alzheimer's disease and can even be utilized in developing therapeutic strategies.