Li Kang, Jia Hengchuan, She Xiaojun, Cui Bo, Zhang Na, Chen Xuewei, Xu Chuanxiang, An Gaihong, Ma Qiang
Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
J Neurol Sci. 2014 May 15;340(1-2):191-7. doi: 10.1016/j.jns.2014.03.027. Epub 2014 Mar 19.
Chronic noise exposure has been associated with abnormalities in glutamate (Glu)-NMDAR signaling and tau hyperphosphorylation. However, further studies are necessary to clarify potential causal relationships. The aim of the present study was to evaluate the role of NMDA receptors in noise-induced tau hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar rats were randomly divided into three groups in the present study: control with isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d × 14d) and treated with saline (n=10); and noise exposure and treated with MK-801 (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202 and Ser396, and proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were measured in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We showed that phosphorylated tau levels were enhanced in noise-exposed-rat hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202 and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise-induced GSK3β overexpression but had no significant effect on PP2A levels. This suggests that MK-801 protects against chronic-noise-induced tau hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that Glu-NMDAR signaling may be involved in triggering aberrant tau hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.
长期噪声暴露与谷氨酸（Glu）-NMDAR信号异常及tau蛋白过度磷酸化有关。然而，需要进一步研究来阐明潜在的因果关系。本研究的目的是评估NMDA受体在大鼠海马体和前额叶皮质噪声诱导的tau蛋白过度磷酸化中的作用。在本研究中，雄性Wistar大鼠被随机分为三组：滴注等渗盐水的对照组（n = 10）；噪声暴露组（100 dB SPL白噪声，4小时/天×14天）并给予盐水处理（n = 10）；噪声暴露组并给予MK-801处理（0.5mg/kg，腹腔注射；n = 10）。在最后一次噪声暴露后，测量海马体和前额叶皮质（PFC）中Ser202和Ser396位点磷酸化的tau蛋白水平，以及参与过度磷酸化的蛋白，即糖原合酶激酶3β（GSK3β）和蛋白磷酸酶2A（PP2A）。我们发现，噪声暴露大鼠的海马体和PFC中磷酸化tau蛋白水平升高。MK-801降低了海马体和PFC中Ser202和Ser396位点tau蛋白的过度磷酸化。此外，MK-801逆转了噪声诱导的GSK3β过表达，但对PP2A水平没有显著影响。这表明MK-801可预防海马体和PFC中慢性噪声诱导的tau蛋白过度磷酸化。这些发现表明，Glu-NMDAR信号可能参与慢性噪声暴露后海马体和PFC中异常tau蛋白过度磷酸化的触发。
