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三聚氰胺通过抑制婴儿大鼠谷氨酸能传递的突触前抑制作用损害空间认知和海马突触可塑性。

Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats.

机构信息

College of Life Sciences and Key Lab of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China.

出版信息

Toxicology. 2011 Nov 18;289(2-3):167-74. doi: 10.1016/j.tox.2011.08.011. Epub 2011 Aug 17.

Abstract

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.

摘要

三聚氰胺污染的丑闻尚未完全平息,因为三聚氰胺的毒性仍然引起公众对健康的关注。众所周知,胎儿和婴儿期在大脑发育中起着最重要的作用,而对于三聚氰胺对儿童中枢神经系统(CNS)的有害影响,研究甚少。在本研究中,我们研究了三聚氰胺对大鼠行为和电生理学改变的影响,并使用全细胞膜片钳技术在幼鼠海马 CA1 神经元中研究了三聚氰胺对突触传递的影响。 Morris 水迷宫(MWM)测试表明,三聚氰胺显着损害了学习和记忆能力。长时程增强(LTP)测试表明,三聚氰胺组的场兴奋性突触后电位(fEPSP)斜率明显低于对照组。此外,全细胞膜片钳实验数据表明,三聚氰胺使自发 EPSC(sEPSC)和 minitura EPSC(mEPSC)的频率均降低了相同的程度(分别约为 76%和 78%)。然而,三聚氰胺加药后 sEPSC 或 mEPSC 幅度或动力学没有明显变化,表明三聚氰胺对谷氨酸能传递的影响可能是突触前的。总之,三聚氰胺降低了海马突触前传递中谷氨酸的释放,这部分导致 LTP 减少,并进一步损害了学习和记忆功能。

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