Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
BMC Neurosci. 2023 Feb 23;24(1):14. doi: 10.1186/s12868-023-00782-8.
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) brain, while the effect of IL-17 on the course of Aβ has not been well defined.
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 neuron damage. At the same time, male C57BL/6 mice were injected with Aβ 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.
Altogether, 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 Aβ mice, the results showed that the level of IL-17 was increased in Aβ model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation the TRAF6/NF-κB pathway.
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 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.
神经炎症在淀粉样蛋白-β（Aβ）发病机制中起着关键作用。细胞因子白细胞介素-17A（IL-17）参与中枢神经系统的学习和记忆过程，其水平在阿尔茨海默病（AD）大脑中报告增加，而 IL-17 对 Aβ 病程的影响尚未得到很好的定义。
在这里，我们使用 APP/PS1 小鼠来检测 IL-17 的表达水平。用 IL-17 处理原代海马神经元，并用免疫荧光法研究 IL-17 是否诱导神经元损伤。同时，雄性 C57BL/6 小鼠注射 Aβ 模拟 Aβ 模型。然后用 IL-17 中和抗体（IL-17Ab）注射侧脑室，并用旷场试验、新物体识别试验、恐惧条件试验检测认知功能。LTP 用于评估突触可塑性，分子生物学技术用于评估 IL-17/TRAF6/NF-κB 通路，ELISA 用于检测炎症因子。
总的来说，我们发现 APP/PS1 小鼠中 IL-17 增加，并用原代海马神经元给予 IL-17 诱导神经损伤。有趣的是，使用 Aβ 小鼠，结果表明 Aβ 模型小鼠中 IL-17 水平增加，IL-17Ab 通过下调 TRAF6/NF-κB 通路可改善 C57BL/6 小鼠 Aβ 诱导的神经毒性和认知下降。
这些发现强调了 IL-17 在 Aβ 诱导的突触功能障碍和认知缺陷中的致病作用。通过下调 TRAF6/NF-κB 通路，抑制 IL-17 可改善 C57BL/6 小鼠 Aβ 诱导的神经毒性和认知下降，为 Aβ 诱导的认知障碍机制提供了新的线索，并为治疗干预提供了依据。
