Specific tau phosphorylation sites in hippocampus correlate with impairment of step-down inhibitory avoidance task in rats
Specific tau phosphorylation sites in hippocampus correlate with impairment of step-down inhibitory avoidance task in rats
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DOI：
10.1016/j.bbr.2004.09.007
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发表时间：
2005-03-30
影响因子：
2.7
通讯作者：
Chen, YG
中科院分区：
文献类型：
--
作者：
Chen, YG
微管相关蛋白tau在阿尔茨海默病（AD）中异常磷酸化，并在神经元缠结（NFT）中聚集为成对螺旋丝（PHF），这是AD的病理特征之一，并且它们的存在与痴呆的严重程度相关。在受影响的神经元中的蛋白磷酸酶功能障碍被认为是AD发展的可能致病因素。我们在这里表明，tau蛋白磷酸化的模式与大鼠大脑记忆保持能力的下降相关。本研究选用55只成年大鼠，采用一次性跳台法，对记忆保持能力正常和低下的大鼠进行了区分。Western blot和/或免疫组化结果显示，在跳台抑制性回避记忆障碍大鼠中，海马tau蛋白Thr 231/Ser 235（M4）位点磷酸化，PP-1表达显著增加，PP-2B表达显著减少。其中暗示：（2）PP-1可能参与了tau蛋白Thr 231和Ser 235位点磷酸化的调节，PP-1含量的上调可能与脑tau蛋白Thr 231/Ser 235位点的过度磷酸化及大鼠记忆力下降有关;（3）PP-2B含量的降低可诱导M4侧tau蛋白的过度磷酸化。(C)2004 Elsevier B. V.保留所有权利。
Microtubule associated protein tau is abnormally phosphorylated in Alzheimer's disease (AD) and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs), which are one of the pathological signatures of AD and their presence correlates with severity of dementia. Dysfunction of protein phosphatases in the effected neurons is proposed to be a possible causative factor to AD development. We show here that the pattern of tau phosphorylation correlates with the decline of memory retention ability in rat brain. In our study, we have chosen 55 rats of full age to conduct the discrimination between their normal and low ability of memory retention in one-trial step-down test. It was found that among rats that developed the impairment in memory retention in step-down inhibitory avoidance task, tau protein in their hippocampus was hyperphosohorylated at Thr231/Ser235 (M4) sites of tau, and the significantly increased expression of PP-1 and the decreased one of PP-2B were also determined by Western blot and/or immunohistochemistry. It is implicated that: (1) the hyperphosphorylation of tau at M4 sites may be crucial to affect the memory retention of elder rats; (2) PP-1 might participate in the regulation of phosphorylation at Thr231 and Ser235 epitope of tau in vivo, and the up-regulation of PP-1 content could be in relation to tau hyperphosphorylation at Thr231/Ser235 sites of brain tau and the worse memory retention of rats indirectly; and (3) the decline of PP-2B content could induced the hyperphosphorylation of tau at M4 sides in vivo. (C) 2004 Elsevier B.V. All rights reserved.