Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats
Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats
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三聚氰胺通过抑制幼年大鼠的突触前谷氨酸能传递来损害空间认知和海马突触可塑性
DOI：
10.1016/j.tox.2011.08.011
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发表时间：
2011-11-18
期刊：
影响因子：
4.5
通讯作者：
Zhang, Tao
中科院分区：
文献类型：
--
作者：
Yang, Jiajia;An, Lei;Zhang, Tao
三聚氰胺污染的丑闻还没有完全平息，因为三聚氰胺的毒性继续引起人们对公共健康的关注。众所周知，胎儿和婴儿期是大脑发育的重要时期，而三聚氰胺对儿童中枢神经系统（CNS）的危害却鲜有报道。本研究观察了三聚氰胺对大鼠行为和电生理的影响，并采用全细胞膜片钳技术观察了三聚氰胺对幼年大鼠海马CA1区神经元突触传递的影响。Morris水迷宫实验表明，三聚氰胺对小鼠的学习记忆能力有明显损害。长时程增强（LTP）实验显示，三聚氰胺组的场兴奋性突触后电位（fEPSP）斜率显著低于对照组。此外，全细胞膜片钳实验数据显示，三聚氰胺降低自发EPSCs（sEPSCs）和小型EPSCs（mEPSCs）的频率在相同程度上（约76%和78%）。然而，三聚氰胺添加后，sEPSC或mEPSC振幅或动力学没有显着变化，表明三聚氰胺对突触能传递的影响可能是突触前的。结论：三聚氰胺降低了海马突触前递质谷氨酸的释放，部分导致LTP降低，进而损害学习记忆功能。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The scandal of melamine-contamination has not been quite blown out, since the toxicity of melamine continues to raise concerns for public health. It has been well known that fetus and infant periods play the most important roles in brain development, whereas little has been done on the harmful effects of melamine on the center nervous system (CNS) of children. In the present study, we investigated the effects of melamine on behavioral and electrophysiology alternations in rats, and the effects of melamine on synaptic transmission were examined using whole-cell patch-clamp technique in the hippocampal CA1 neurons of infant rats. Morris water maze (MWM) test showed that learning and memory abilities were impaired significantly by melamine. The long-time potentiation (LTP) test exhibited that the field excitatory postsynaptic potential (fEPSP) slopes were significantly lower in melamine group compared to that in control group. Furthermore, the data of whole-cell patch-clamp experiments showed that melamine decreased the frequencies of both spontaneous EPSCs (sEPSCs) and minitura EPSCs (mEPSCs) to the same extent (about 76% and 78% respectively). However, there were no significant changes in sEPSC or mEPSC amplitude or kinetics after melamine addition, indicating that the effect of melamine on glutamatergic transmission was probably presynaptic. In conclusion, melamine reduced the release of glutamate in presynaptic transmission of hippocampus, which partly resulted in diminished LTP and further damaged the function of learning and memory. (C) 2011 Elsevier Ireland Ltd. All rights reserved.