Data_Sheet_1_Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice.ZIP

Abnormal synaptic transmission leads to learning and memory disorders and is the main feature of neurological diseases. Sorting nexin 27 (SNX27) is an endosomal adaptor protein associated with a variety of nervous system diseases, and it is mainly responsible for the trafficking of postsynaptic membrane receptors. However, the roles of SNX27 in regulating synaptic and cognitive function are not fully understood. Here, we first generated a neuron-specific human-SNX27 transgenic mouse model (hSNX27 Tg) that exhibited enhanced excitatory synaptic transmission and long-term potentiation (LTP). In addition, we found that the hSNX27 Tg mice displayed enhanced learning and memory, lower-level anxiety-like behavior, and increased social interaction. Furthermore, we found that SNX27 overexpression upregulated the expression of glutamate receptors in the cortex and hippocampus of hSNX27 Tg mice. Together, these results indicate that SNX27 overexpression promotes synaptic function and cognition through modulating glutamate receptors.

异常突触传递可引发学习记忆障碍，亦是神经系统疾病的核心特征之一。分拣蛋白27（Sorting nexin 27，SNX27）是一类与多种神经系统疾病相关的内体衔接蛋白，主要负责突触后膜受体的转运过程。然而，SNX27在调控突触功能与认知功能中的具体作用尚未完全阐明。本研究首先构建了神经元特异性人源SNX27转基因小鼠模型（hSNX27 Tg），该模型的兴奋性突触传递与长时程增强（long-term potentiation，LTP）水平均显著增强。此外，本研究发现hSNX27 Tg小鼠的学习记忆能力显著提升，焦虑样行为水平降低，且社交互动行为增多。进一步实验显示，SNX27过表达可上调hSNX27 Tg小鼠大脑皮层与海马体内谷氨酸受体的表达水平。综上，上述研究结果表明，SNX27过表达可通过调控谷氨酸受体的表达，进而促进突触功能与认知能力的提升。