Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Cell Rep. 2021 Dec 7;37(10):110094. doi: 10.1016/j.celrep.2021.110094.
Cognitive impairment (CI) is a disabling concomitant of multiple sclerosis (MS) with a complex and controversial pathogenesis. The cytokine interleukin-17A (IL-17A) is involved in the immune pathogenesis of MS, but its possible effects on synaptic function and cognition are still largely unexplored. In this study, we show that the IL-17A receptor (IL-17RA) is highly expressed by hippocampal neurons in the CA1 area and that exposure to IL-17A dose-dependently disrupts hippocampal long-term potentiation (LTP) through the activation of its receptor and p38 mitogen-activated protein kinase (MAPK). During experimental autoimmune encephalomyelitis (EAE), IL-17A overexpression is paralleled by hippocampal LTP dysfunction. An in vivo behavioral analysis shows that visuo-spatial learning abilities are preserved when EAE is induced in mice lacking IL-17A. Overall, this study suggests a key role for the IL-17 axis in the neuro-immune cross-talk occurring in the hippocampal CA1 area and its potential involvement in synaptic dysfunction and MS-related CI.
认知障碍（CI）是多发性硬化症（MS）的一种致残伴随症状，其发病机制复杂且存在争议。细胞因子白细胞介素-17A（IL-17A）参与 MS 的免疫发病机制，但它对突触功能和认知可能产生的影响在很大程度上仍未得到探索。在这项研究中，我们表明白细胞介素-17A 受体（IL-17RA）在 CA1 区的海马神经元中高度表达，并且 IL-17A 的暴露通过其受体和 p38 丝裂原活化蛋白激酶（MAPK）的激活，可使海马长时程增强（LTP）呈剂量依赖性地受到破坏。在实验性自身免疫性脑脊髓炎（EAE）期间，IL-17A 的过表达与海马 LTP 功能障碍相平行。体内行为分析表明，在缺乏 IL-17A 的小鼠中诱导 EAE 时，可保留视觉空间学习能力。总的来说，这项研究表明，IL-17 轴在海马 CA1 区发生的神经免疫相互作用中起着关键作用，其可能与突触功能障碍和 MS 相关的 CI 有关。
