Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
Toxicol Sci. 2018 Jun 1;163(2):385-396. doi: 10.1093/toxsci/kfx039.
Converging evidence supported that melamine could impair learning and memory and hippocampal function by mechanisms as yet unknown. The aim of this study was to obtain the first clues of how melamine affected spatial cognition, and how it may act on hippocampal function to modulate plasticity. Morris water maze test was used to probe spatial learning and memory. Pharmacological approaches were employed to modulate NMDAR and AMPAR-dependent long-term synaptic plasticity of rats' hippocampal CA1 region. Both systemic and intrahippocampal application of melamine impaired the formation of long-term spatial memory, particularly consolidation memory. The reduced expression of NMDA-NR1 and -NR2B subunits, but not AMPAR subunits, was presented. Meanwhile melamine inhibited inductions of long-term potentiation (LTP) and long-term depression (LTD) via mediating NMDARs. Notably, the specific role of hippocampal CA1 LTD in regulation of spatial consolidation has been observed in normal physiology. Moreover, the prevention of inhibited hippocampal CA1 LTD but not LTP could rescue the disruption of long-term spatial memory of the melamine-treated rats. Taken together, our findings suggested that acute melamine exposure impaired spatial memory consolidation via disrupting hippocampal NMDAR-dependent LTD. This provided an important insight into the neurophysiology of melamine-related and other psychiatric disorders.
越来越多的证据表明，三聚氰胺可能通过未知的机制损害学习和记忆以及海马功能。本研究旨在获得三聚氰胺如何影响空间认知的第一个线索，以及它如何作用于海马功能来调节可塑性。我们使用 Morris 水迷宫测试来探测空间学习和记忆。采用药理学方法调节大鼠海马 CA1 区 NMDA 受体和 AMPA 受体依赖性长时程突触可塑性。三聚氰胺的全身和海马内给药均损害了长期空间记忆的形成，特别是巩固记忆。NMDA-NR1 和 -NR2B 亚基的表达减少，但 AMPA 亚基没有减少。同时，三聚氰胺通过调节 NMDAR 抑制长时程增强（LTP）和长时程抑制（LTD）的诱导。值得注意的是，在正常生理条件下，海马 CA1 LTD 在调节空间巩固中的特定作用已经被观察到。此外，预防抑制的海马 CA1 LTD 而不是 LTP 可以挽救三聚氰胺处理大鼠长期空间记忆的破坏。总之，我们的研究结果表明，急性三聚氰胺暴露通过破坏海马 NMDA 受体依赖性 LTD 损害空间记忆的巩固。这为三聚氰胺相关和其他精神疾病的神经生理学提供了重要的见解。
