Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex
Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex
复制标题
慢性噪音暴露导致大鼠海马和前额叶皮层 Tau 蛋白过度磷酸化持续存在以及 NFT Tau 蛋白的形成
DOI：
10.1016/j.expneurol.2012.08.028
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发表时间：
2012-12-01
影响因子：
5.3
通讯作者：
Liu, Hongtao
中科院分区：
文献类型：
--
作者：
Cui, Bo;Zhu, Lixing;Liu, Hongtao
噪声暴露对中枢神经系统的非听觉效应已在流行病学和实验上得到证实。慢性噪声暴露（CNE）与tau蛋白过度磷酸化和阿尔茨海默病（AD）样病理改变有关。然而，这些协会的实验证据仍然有限。本研究的目的是探讨CNE [100 dB声压级（SPL）白色噪声的影响。4 h/d × 14 d]对大鼠海马和前额皮质中tau蛋白磷酸化的影响。将48只雄性Wistar大鼠随机分为两组：噪声暴露组和对照组。在最后一次噪声暴露结束后的不同时间点（第0、3、7和14天）测量海马和前额皮质中Ser 202、Ser 396、Ser 404和Ser 422处的放射免疫沉淀测定（RIPA）可溶性和RIPA不溶性磷酸化tau蛋白的水平。连续14天暴露于白色噪声显著增加了海马和前额皮质中的tau蛋白在Ser 202、Ser 396、Ser 404和Ser 422处的磷酸化水平，这些位点通常在AD脑中磷酸化。Tau蛋白的过度磷酸化在噪声暴露停止后持续7 ~ 14 d。这些变化也伴随着病理性神经元缠结（NFT）tau蛋白的产生后3，7和14 d的刺激结束。此外，发现参与过度磷酸化的蛋白质（即糖原合成酶激酶3 β（GSK 3 β）和蛋白磷酸酶2A（PP 2A））的持续增加与tau过度磷酸化的增加密切相关。这项研究的结果表明，CNE导致非NFT过度磷酸化tau蛋白的长期增加，并延迟海马和前额皮质中错误折叠的NFT tau蛋白的形成。我们的研究结果还提供了证据，GSK 3 β和PP 2A参与这些过程。(C)2012 Elsevier Inc. All rights reserved.
The non-auditory effects of noise exposure on the central nervous system have been established both epidemiologically and experimentally. Chronic noise exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes. However, experimental evidence for these associations remains limited. The aim of the current study was to explore the effects of CNE [100 dB sound pressure level (SPL) white noise. 4 h/d x 14 d] on tau phosphorylation in the rat hippocampus and the prefrontal cortex. Forty-eight male Wistar rats were randomly assigned to two groups: a noise-exposed group and a control group. The levels of radioimmunoprecipitation assay (RIPA)-soluble and RIPA-insoluble phosphorylated tau at Ser202, Ser396, Ser404, and Ser422 in the hippocampus and the prefrontal cortex were measured at different time points (days 0, 3, 7, and 14) after the end of the last noise exposure. Exposure to white noise for 14 consecutive days significantly increased the levels of tau phosphorylation at Ser202, Ser396, Ser404, and Ser422, the sites typically phosphorylated in AD brains, in the hippocampus and the prefrontal cortex. Tau hyperphosphorylation persisted for 7 to 14d after the cessation of noise exposure. These alterations were also concomitant with the generation of pathological neurofibrillary tangle (NFT) tau 3, 7 and 14 d after the end of the stimulus. Furthermore, lasting increases in proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3 beta (GSK3 beta) and protein phosphatase 2A (PP2A), were found to occur in close correspondence with increase in tau hyperphosphorylation. The results of this study show that CNE leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our results also provide evidence for the involvement of GSK3 beta and PP2A in these processes. (C) 2012 Elsevier Inc. All rights reserved.