An okadaic acid-induced model of tauopathy and cognitive deficiency.
An okadaic acid-induced model of tauopathy and cognitive deficiency.
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DOI：
10.1016/j.brainres.2010.08.077
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发表时间：
2010-11-04
期刊：
影响因子：
2.9
通讯作者：
Simpkins JW
中科院分区：
文献类型：
--
作者：
Zhang Z;Simpkins JW
阿尔茨海默病（Alzheimer's disease，AD）是一种进行性神经退行性疾病，可导致老年人认知和行为功能的退化。神经元缠结（NFT）是AD的病理学标志之一，已显示其与AD患者的新皮层中的痴呆的严重程度正相关。在试图表征体内AD tau蛋白病模型的过程中，将蛋白磷酸酶抑制剂冈田酸（OA）微注入去卵巢成年大鼠的右侧背海马区。OA治疗组大鼠出现认知缺陷，但运动功能无变化。银染和免疫组化染色均显示OA处理诱导皮质和海马中的NFT样构象变化。大脑这些区域的磷酸化tau以及细胞周期蛋白依赖性激酶5（cdk 5）及其辅激活因子p25显着增加。通过蛋白质羰基化和脂质过氧化来测量，OA处理也增加了氧化应激。这些数据表明，单侧微输注OA到背侧海马引起认知缺陷，NFT样病理变化，和氧化应激，如在AD病理中所见，通过抑制蛋白磷酸酶引起的tau过度磷酸化。
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes cognitive and behavioral deterioration in the elderly. Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of AD that has been shown to correlate positively with the severity of dementia in the neocortex of AD patients. In an attempt to characterize an in vivo AD tauopathy model, okadaic acid (OA), a protein phosphatase inhibitor, was microinfused into the right lateral dorsal hippocampus area of ovariectomized adult rat. Cognitive deficiency was seen in OA-treated rats without a change in motor function. Both silver staining and immunohistochemistry staining revealed that OA treatment induces NFTs-like conformational changes in both the cortex and hippocampus. Phosphorylated tau as well as cyclin-dependent kinase 5 (cdk5) and its coactivator, p25, were significantly increased in these regions of the brain. Oxidative stress was also increased with OA treatment as measured by protein carbonylation and lipid peroxidation. These data suggest that the unilateral microinfusion of OA into the dorsal hippocampus causes cognitive deficiency, NFTs-like pathological changes, and oxidative stress as seen in AD pathology via tau hyperphosphorylation caused by inhibition of protein phosphatases.
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影响因子：
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作者：
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