长期噪声暴露对海马NMDAR2B及Tau蛋白磷酸化影响

Long-term noise exposure causes abnormality of NMDAR2B expression and tau hyperphosphorylation and induction of apoptosis in rat hippocampus

目的探讨长期噪声暴露对大鼠海马的影响及其机制。方法 24只雄性SD大鼠分为对照组与噪声暴露组(100 dB,白噪声,4 h/d×30 d),检测噪声暴露组动物中海马的N-甲基-D-天冬氨酸受体2B亚基(NR2B)的表达和tau蛋白的磷酸化状态;为了探讨其可能机制,用DNA断裂原位末端标记法检测海马神经细胞凋亡状态。结果长期噪声暴露后,实验组与对照组相比海马中NR2B的表达下降达41%,tau蛋白发生过度磷酸化的程度升高2.1倍和海马神经细胞凋亡数量占总神经元细胞数量的0.5%～1%;免疫组织化学结果显示海马中tau蛋白发生过度磷酸化的区域主要在齿状回(DG)区和安蒙氏角(CA)1区。结论长期噪声暴露引起大鼠神经递质系统异常及tau蛋白过度磷酸化可能诱发神经细胞凋亡和认知障碍。

Objective To explore the effects and mechanism of long-term noise exposure on hippocampus of rats. Methods Twenty four male Sprague-Dawley （SD） rats were grouped as control and noise exposure group. Expression of N-methyl-D-aspartic acid receptor 2B subunit（NR2B） and the level of phosphorylation of tau in hippocampus were measured after chronic noise exposure（ 100 dB SPL white noise, 4 hours per day for 30 days）. To explore the possible mechanism,we also detected neuronal cell apoptosis in hippocampus by terminal deoxynucleotidyl transfease-mediated dUTP nick end-labeling（TUNEL） reactivity. Results After long-term noise exposure, the expression of NR2B in the hippocampus decreased by 41%. Meanwhile, the chronic noise exposure also caused tau hyperphosphorylation, which was twice higher than the normal, and neuronal cell apoptosis accounted for 0. 5 % - 1% total neuronal cells in the hippocampus. Immunohistochemistry assaies confirmed that tau hyperphosphorylation was most prominent in dentate gyrus （DG） and CA1 region in the hippcampus. Conclusion Long-term noise exposure induces abnormality of neurotransmitter system and hyperpbosphorylation of tau and the adverse effects could lead to neuronal cell apoptosis and cognition impairment.