Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity

BMC Neuroscience

Research

Yang Meng¹  Juanjuan Yan²  Chenliang Zhou²  Cuiping Guo³  Yulan Liu⁴  Weiguo Dong⁵ 

[1] Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China;Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, China;Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China;Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China;Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China;Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China;Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China;Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China;Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China;Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China;

关键词: IL-17;    Amyloid-β;    IL-17Ab;    Synaptic dysfunction;    Cognitive decline;   

DOI  :  10.1186/s12868-023-00782-8

 received in 2022-09-30, accepted in 2023-02-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNeuroinflammation plays a critical role in Amyloid-β (Aβ) pathophysiology. The cytokine, interleukin-17A (IL-17) is involved in the learning and memory process in the central nervous system and its level was reported to be increased in Alzheimer's disease (AD) brain, while the effect of IL-17 on the course of Aβ has not been well defined. MethodsHere, we used APP/PS1 mice to detect the IL-17 expression level. Primary hippocampal neurons were treated with IL-17, and immunofluorescence was used to investigate whether IL-17 induced neuron damage. At the same time, male C57BL/6 mice were injected with Aβ42 to mimic the Aβ model. Then IL-17 neutralizing antibody (IL-17Ab) was used to inject into the lateral ventricle, and the Open field test, Novel Objective Recognition test, Fear condition test were used to detect cognitive function. LTP was used to assess synaptic plasticity, molecular biology technology was used to assess the IL-17/TRAF6/NF-κB pathway, and ELISA was used to detect inflammatory factors.ResultsAltogether, we here found that IL-17 was increased in APP/PS1 mice, and it induced neural damage by the administration to primary hippocampal neurons. Interestingly, Using Aβ42 mice, the results showed that the level of IL-17 was increased in Aβ42 model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation the TRAF6/NF-κB pathway.ConclusionThese findings highlight the pathogenic role of IL-17 in Aβ induced-synaptic dysfunction and cognitive deficits. Inhibition of IL-17 could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation of the TRAF6/NF-κB pathway, which provides new clues for the mechanism of Aβ-induced cognitive impairments, and a basis for therapeutic intervention.

【 授权许可】

CC BY   
© The Author(s) 2023

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