Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, 381 Nanchen Road, Shanghai, 200444, China.
Neurochem Res. 2019 Nov;44(11):2499-2505. doi: 10.1007/s11064-019-02866-6. Epub 2019 Sep 17.
The hippocampus is critical for memory and emotion and both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors are known to contribute for those processes. However, the underlying molecular mechanisms remain poorly understood. We have previously found that mice undergo memory decline upon dcf1 deletion through ES gene knockout. In the present study, a nervous system-specific dcf1 knockout (NKO) mouse was constructed, which was found to present severely damaged neuronal morphology. The damaged neurons caused structural abnormalities in dendritic spines and decreased synaptic density. Decreases in hippocampal NMDA and AMPA receptors of NKO mice lead to abnormal long term potentiation (LTP) at DG, with significantly decreased performance in the water maze, elevated- plus maze, open field and light and dark test. Investigation into the underlying molecular mechanisms revealed that dendritic cell factor 1 (Dcf1) contributes for memory and emotion by regulating NMDA and AMPA receptors. Our results broaden the understanding of synaptic plasticity's role in cognitive function, thereby expanding its known list of functions.
海马体对于记忆和情绪都至关重要，已知 N-甲基-D-天冬氨酸 (NMDA) 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 受体都有助于这些过程。然而，其潜在的分子机制仍知之甚少。我们之前发现，通过 ES 基因敲除，dcfl 缺失的小鼠会出现记忆衰退。在本研究中，构建了一种神经系统特异性的 dcf1 敲除 (NKO) 小鼠，发现其神经元形态严重受损。受损的神经元导致树突棘的结构异常，并减少了突触密度。NKO 小鼠海马体的 NMDA 和 AMPA 受体减少导致 DG 中的长时程增强 (LTP) 异常，水迷宫、高架十字迷宫、旷场和明暗试验的表现明显下降。对潜在分子机制的研究表明，树突细胞因子 1 (Dcf1) 通过调节 NMDA 和 AMPA 受体来促进记忆和情绪。我们的结果拓宽了对突触可塑性在认知功能中的作用的理解，从而扩大了其已知的功能列表。
