突变型tau蛋白局部基因转移后神经原纤维缠结的快速形成
Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau.
作者信息
Klein Ronald L, Lin Wen-Lang, Dickson Dennis W, Lewis Jada, Hutton Michael, Duff Karen, Meyer Edwin M, King Michael A
机构信息
Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
出版信息
Am J Pathol. 2004 Jan;164(1):347-53. doi: 10.1016/S0002-9440(10)63124-0.
Abstract
Neurofibrillary pathology was produced in the brains of adult rats after localized gene transfer of human tau carrying the P301L mutation, which is associated with frontotemporal dementia with parkinsonism. Within 1 month of in situ transfection of the basal forebrain region of normal rats, tau-immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions had features of neurofibrillary tangles and tau immunoreactivity at light and electron microscopic levels. In addition to neurofibrillary tangles, other tau pathology, including pretangles and neuropil threads, was abundant and widespread. Tau gene transfer to the hippocampal region of amyloid-depositing transgenic mice produced pretangles and threads, as well as intensely tau-immunoreactive neurites in amyloid plaques. The ability to produce neurofibrillary pathology in adult rodents makes this a useful method to study tau-related neurodegeneration.
摘要
携带与帕金森病性额颞叶痴呆相关的P301L突变的人tau蛋白进行局部基因转移后，成年大鼠脑内产生了神经原纤维病理变化。在正常大鼠基底前脑区域原位转染后1个月内，形成了tau免疫反应性和嗜银性神经元病变。在光镜和电镜水平上，纤维状病变具有神经原纤维缠结和tau免疫反应性的特征。除神经原纤维缠结外，其他tau病理变化，包括前缠结和神经毡丝，丰富且广泛。将tau基因转移到淀粉样蛋白沉积转基因小鼠的海马区域会产生前缠结和神经毡丝，以及淀粉样斑块中强烈的tau免疫反应性神经突。在成年啮齿动物中产生神经原纤维病理变化的能力使其成为研究tau相关神经退行性变的有用方法。
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