Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity
Abstract Background Neuroinflammation 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-023-00782-8 |
| _version_ | 1797577874328256512 |
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| author | Yulan Liu Yang Meng Chenliang Zhou Juanjuan Yan Cuiping Guo Weiguo Dong |
| author_facet | Yulan Liu Yang Meng Chenliang Zhou Juanjuan Yan Cuiping Guo Weiguo Dong |
| author_sort | Yulan Liu |
| collection | DOAJ |
| description | Abstract Background Neuroinflammation 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. Methods Here, 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. Results Altogether, 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. Conclusion These 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. |
| first_indexed | 2024-03-10T22:15:15Z |
| format | Article |
| id | doaj.art-441c3e4c764541c5a32ff51b1f830b19 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-03-10T22:15:15Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-441c3e4c764541c5a32ff51b1f830b192023-11-19T12:28:41ZengBMCBMC Neuroscience1471-22022023-02-0124111210.1186/s12868-023-00782-8Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicityYulan Liu0Yang Meng1Chenliang Zhou2Juanjuan Yan3Cuiping Guo4Weiguo Dong5Department of Critical Care Medicine, Renmin Hospital of Wuhan UniversityCentral Laboratory, Renmin Hospital of Wuhan UniversityDepartment of Critical Care Medicine, Renmin Hospital of Wuhan UniversityDepartment of Critical Care Medicine, Renmin Hospital of Wuhan UniversityDepartment of Critical Care Medicine, Renmin Hospital of Wuhan UniversityDepartment of Gastroenterology, Renmin Hospital of Wuhan UniversityAbstract Background Neuroinflammation 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. Methods Here, 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. Results Altogether, 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. Conclusion These 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.https://doi.org/10.1186/s12868-023-00782-8IL-17AβIL-17AbSynaptic dysfunctionCognitive decline |
| spellingShingle | Yulan Liu Yang Meng Chenliang Zhou Juanjuan Yan Cuiping Guo Weiguo Dong Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity BMC Neuroscience IL-17 Aβ IL-17Ab Synaptic dysfunction Cognitive decline |
| title | Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity |
| title_full | Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity |
| title_fullStr | Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity |
| title_full_unstemmed | Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity |
| title_short | Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity |
| title_sort | activation of the il 17 traf6 nf κb pathway is implicated in aβ induced neurotoxicity |
| topic | IL-17 Aβ IL-17Ab Synaptic dysfunction Cognitive decline |
| url | https://doi.org/10.1186/s12868-023-00782-8 |
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