AMPA受体
神经科学
小胶质细胞
内生
突触可塑性
星形胶质细胞
阿尔茨海默病
受体
发病机制
生物
心理学
医学
中枢神经系统
疾病
谷氨酸受体
免疫学
内分泌学
内科学
炎症
作者
Kongjie Lu,Chenyang Li,Jiao Liu,Jinpeng Wang,Yongfeng Li,Bin He,Junzhao Li,Xiaochen Zhang,Mengping Wei,Yonglu Tian,Rong Zhang,Chen Zhang,Yong Zhang
标识
DOI:10.1073/pnas.2303878120
摘要
AMPA receptors (AMPARs) play a critical role in synaptic plasticity and learning and memory, and dysfunction or dysregulation of AMPARs could lead to various neurological and psychiatric disorders, such as Alzheimer's disease (AD). However, the dynamics and/or longitudinal changes of AMPARs in vivo during AD pathogenesis remain elusive. Here, employing 5xFAD SEP-GluA1 KI mice, we investigated endogenous AMPA receptor dynamics in a whisker deflection-associated Go/No-go learning paradigm. We found a significant increase in synaptosomal AMPA receptor subunits GluA1 in WT mice after learning, while no such changes were detected in 7-mo-old 5xFAD mice. Daily training led to an increase in endogenous spine surface GluA1 in Control mice, while this increase was absent in 5xFAD-KI mice which correlates with its learning defects in Go/No-go paradigm. Furthermore, we demonstrated that the onset of abnormal AMPAR dynamics corresponds temporally with microglia and astrocyte overactivation. Our results have shown that impairments in endogenous AMPA receptor dynamics play an important role in learning deficits in 5xFAD mice and AD pathogenesis.
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