单位：[1]Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China华中科技大学同济医学院附属同济医院麻醉科[2]Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China华中科技大学同济医学院附属同济医院放射科
Growing evidences indicate that neuropathic pain is frequently accompanied with cognitive impairments, which aggravate the decrease in the quality of life of chronic pain patients. Furthermore, it has been shown that the activation of Glucagon-like-peptide-1receptor (GLP-1R) improved memory deficit in multiple diseases, including Alzheimer's disease (AD), stroke. However, whether GLP-1R activation could improve memory impairment induced by neuropathic pain and the mechanisms underlying the effect of the activation of GLP-1R on memory protection have not yet been established. The spared nerve injury (SNI) model was established as a kind of neuropathic pain. And novel-object recognition memory (hippocampus-dependent memory) was tested by the novel object recognition test (NORT). The expression levels of GLP-1, GLP-1R, adenosine monophosphateactivated protein kinase (AMPK), p-AMPKThr172, nuclear factor kappa B p65 (NF-kappa B p65), interleukin-1beta (IL1 beta), IL-1 beta p17 (mature IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and the synaptic proteins were tested in the murine hippocampus with memory deficits caused by neuropathic pain. Then, exenatide acetate (Ex-4, a GLP-1R agonist), exendin (9-39) (Ex(9-39), a GLP-1R antagonist) and Compound C dihydrochloride (CC, an AMPK inhibitor) were used to test the effects of the activation of GLP-1R in the mice with neuropathic pain. First, we uncovered that neuropathic pain could inhibit GLP-1/GLP-R axis, disturb inflammatory signaling pathway, increase the expression of IL-1 beta, IL-1 beta p17 and TNF-alpha, downregulate the synaptic proteins (postsynaptic density protein 95 (PSD95) and Arc). Subsequently, we reported that Ex-4 treatment could improve recognition memory impairment, increase the ratio of p-AMPKThr172/AMPK, inhibit the phosphorylation NF-kappa B p65 and decrease the expression of IL-1 beta, IL-1 beta p17 and TNF-alpha, upregulate the levels of PSD95 and Arc. Moreover, we found that Ex (9-39) and CC treatment could abrogate the memory protection of activation of GLP-1R in mice with neuropathic pain. The results indicated that the activation of GLP-1R could improve recognition memory impairment via regulating AMPK/NF-kappa B pathway, improving neuroinflammation, reversing the decreased level of synaptic proteins in neuropathic pain mice.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81974170]
第一作者单位：[1]Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
通讯作者：
通讯机构：[1]Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China[*1]Jiefang avnue1095#, Wuhan, Hubei 430030, China.
推荐引用方式(GB/T 7714)：
Zhang Long-Qing,Zhang Wen,Li Ting,et al.GLP-1R activation ameliorated novel-object recognition memory dysfunction via regulating hippocampal AMPK/NF-kappa B pathway in neuropathic pain mice[J].NEUROBIOLOGY OF LEARNING AND MEMORY.2021,182:doi:10.1016/j.nlm.2021.107463.
APA：
Zhang, Long-Qing,Zhang, Wen,Li, Ting,Yang, Ting,Yuan, Xiaoman...&Tian, Xue-Bi.(2021).GLP-1R activation ameliorated novel-object recognition memory dysfunction via regulating hippocampal AMPK/NF-kappa B pathway in neuropathic pain mice.NEUROBIOLOGY OF LEARNING AND MEMORY,182,
MLA：
Zhang, Long-Qing,et al."GLP-1R activation ameliorated novel-object recognition memory dysfunction via regulating hippocampal AMPK/NF-kappa B pathway in neuropathic pain mice".NEUROBIOLOGY OF LEARNING AND MEMORY 182.(2021)
