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人类基因的过表达通过调节小鼠的突触可塑性增强学习和记忆。

Overexpression of Human Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice.

作者信息

Huo Yuanhui, Gao Yue, Zheng Qiuyang, Zhao Dongdong, Guo Tiantian, Zhang Shuo, Zeng Yuzhe, Cheng Yiyun, Gu Huaping, Zhang Lishan, Zhu Bin, Luo Hong, Zhang Xian, Zhou Ying, Zhang Yun-Wu, Sun Hao, Xu Huaxi, Wang Xin

机构信息

State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.

National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, China.

出版信息

Front Cell Dev Biol. 2020 Nov 27;8:595357. doi: 10.3389/fcell.2020.595357. eCollection 2020.

Abstract

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- transgenic mouse model (h Tg) that exhibited enhanced excitatory synaptic transmission and long-term potentiation (LTP). In addition, we found that the h 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 h Tg mice. Together, these results indicate that SNX27 overexpression promotes synaptic function and cognition through modulating glutamate receptors.

摘要

异常的突触传递会导致学习和记忆障碍,是神经疾病的主要特征。分选连接蛋白27(SNX27)是一种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运输。然而,SNX27在调节突触和认知功能中的作用尚未完全明确。在此,我们首先构建了一种神经元特异性人类转基因小鼠模型(h Tg),该模型表现出增强的兴奋性突触传递和长时程增强(LTP)。此外,我们发现h Tg小鼠表现出增强的学习和记忆能力、较低水平的焦虑样行为以及增加的社交互动。此外,我们发现SNX27的过表达上调了h Tg小鼠皮层和海马中谷氨酸受体的表达。这些结果共同表明,SNX27的过表达通过调节谷氨酸受体来促进突触功能和认知。

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