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;    Aβ;    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) brains, 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 neuronal 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 injected into the lateral ventricle, and the open-field test, novel objective recognition test, and fear conditioning test were used to detect cognitive function. Long-term potentiation (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 found that IL-17 was increased in APP/PS1 mice and induced neural damage by 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 10 C57BL/6 mice by downregulating 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 downregulating the TRAF6/NF-κB pathway, which provides new clues for the mechanism of Aβ-induced cognitive impairments.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023. corrected publication 2023

【 图 表 】

12888_2023_5113_Article_IEq2.gif

13690_2023_1172_Article_IEq6.gif

Fig. 1

Fig. 3

42490_2023_74_Article_IEq25.gif

Fig. 2