Arendt T, Hanisch F, Holzer M, Brückner M K
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
Neuroreport. 1994 Jun 27;5(11):1397-400.
In vivo phosphorylation was stimulated in the rat basal nucleus by stereotaxic injection of the phosphatase inhibitor okadaic acid (OA). Hyperphosphorylation of neurofilaments and of the microtubule-associated proteins tau and MAP2 was associated with their redistribution from the axonal compartment into the cell bodies of large projection neurones where they appeared as paired helical filament (PHF)-like immunoreactivity. Astrocytes showed a dramatic increase in APP immunoreactivity and changed their appearance to a stellate shape with long processes. The results demonstrate that abnormal tau phosphorylation and changes in the expression and/or metabolism of APP can be induced in vivo by altering protein phosphorylation. The present experimental paradigm might, therefore, provide a useful tool to model early steps of the pathomechanism of Alzheimer's disease.
通过立体定位注射磷酸酶抑制剂冈田酸（OA）刺激大鼠基底核中的体内磷酸化。神经丝以及微管相关蛋白tau和MAP2的过度磷酸化与它们从轴突区室重新分布到大型投射神经元的细胞体有关，在这些细胞体中它们呈现出成对螺旋丝（PHF）样免疫反应性。星形胶质细胞的淀粉样前体蛋白（APP）免疫反应性显著增加，并转变为具有长突起的星状形态。结果表明，通过改变蛋白质磷酸化可在体内诱导异常的tau磷酸化以及APP表达和/或代谢的变化。因此，目前的实验范式可能为模拟阿尔茨海默病发病机制的早期步骤提供一个有用的工具。
