JADE2 Is Essential for Hippocampal Synaptic Plasticity and Cognitive Functions in Mice
JADE2 Is Essential for Hippocampal Synaptic Plasticity and Cognitive Functions in Mice
复制标题
JADE2 对于小鼠海马突触可塑性和认知功能至关重要
DOI：
10.1016/j.biopsych.2022.05.021
复制
发表时间：
2022-10-17
影响因子：
10.6
通讯作者：
Huang, Zhuo
中科院分区：
文献类型：
--
作者：
Fan, Minghua;Liu, Yongqing;Huang, Zhuo
BACKGROUND: Impairment of synaptic plasticity is closely correlated with a range of pathological conditions, such as cognitive deficits. However, how synaptic efficacy is regulated remains incompletely understood. Here, we report that the epigenetic factor JADE2 was indispensable for the maintenance of hippocampal synaptic plasticity and cognitive functions in mice.METHODS: We used the Morris water maze and the fear conditioning test to examine learning-related behaviors. In addition, Western blotting, viral-mediated JADE2 manipulations, RNA sequencing, and electrophysiological recordings were used to address our questions. RESULTS: JADE2 expression is increased upon enhanced neuronal activity in vitro and in vivo. Knockdown or ge-netic deletion of Jade2 in hippocampal CA1 results in impaired structural and functional synaptic plasticity, leading to memory impairment, whereas overexpression of JADE2 in CA1 neurons facilitates hippocampal-dependent learning and memory. Mechanistically, our data show that JADE2 modulates synaptic functions mainly by transcriptional activation of cytoskeletal regulator Rac1, and this activity is dependent on its interaction with histone acetyltransferase HBO1. Finally, we demonstrate that restoring RAC1 expression in Jade2 knockout mice could rescue the deficits in synaptic plasticity and learning-related behaviors.CONCLUSIONS: Our findings reveal that JADE2 plays a critical role in regulating synaptic plasticity and memory formation, suggesting that activity-dependent epigenetic regulation is an important molecular mechanism in controlling synaptic plasticity.
