突触可塑性
长时程增强
海马体
神经科学
SNi公司
海马结构
神经可塑性
基因敲除
恐惧条件反射
下调和上调
慢性疼痛
生物
医学
内科学
细胞凋亡
生物化学
受体
扁桃形结构
基因
水解
酸水解
作者
Y. Liu,Qiang Liu,Wang Hai-bi,Yongkang Qiu,Jia-Tao Lin,Weifeng Wu,Ning Wang,Dong Wang,Jie Wan,Chen Chen,Shuai Li,Hui Zheng,Yuqing Wu
摘要
Abstract Aims Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain. Methods We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long‐term potentiation (LTP). In the intervention study, AAV9‐CaMKIIα‐Cre‐EGFP was injected to SIRT1 flox/flox mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9‐CaMKIIα‐SIRT1‐3*Flag‐GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1. Results Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity. Conclusions Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.
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