OBJECTIVE Autoantibodies against ribosomal P proteins (anti-P antibodies) are strongly associated with the neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE). The present study was designed to assess whether anti-P antibodies can induce abnormal brain electrical activities in mice and investigate the potential cytopathological mechanism. METHODS Affinity-purified human anti-ribosomal P antibodies were injected intravenously into mice after blood-brain barrier (BBB) disruption. The auditory steady-state response (ASSR) was evaluated based on electroencephalography (EEG) signals in response to 40-Hz click-train stimuli, which were recorded from electrodes implanted in the skull of mice. Immunofluorescence staining was used to examine the morphology and density of neurons and glia in the hippocampus and cortex. The presence of apoptosis in the brain tissues was studied using the TUNEL assay. A PLX3397 diet was used to selectively eliminate microglia from the brains of mice. RESULTS Circulating anti-P antibodies caused an enhancement of the ASSR and the activation of microglia through the disrupted BBB, while no obvious neural apoptosis was observed. In contrast, when microglia were depleted, anti-P antibodies induced a serious reduction in the ASSR and neural apoptosis. CONCLUSION Our study indicates that anti-P antibodies can directly induce the dysfunction of auditory-evoked potentials in the brain and that microglia are involved in the protection of neural activity after the invasion of anti-P antibodies, which could have important implications for NPSLE.

中文翻译：

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小胶质细胞对天真的小鼠SLE患者抗P IgG诱导的听觉稳态反应受损的神经保护作用。

目的针对核糖体P蛋白的自身抗体（抗P抗体）与系统性红斑狼疮（NPSLE）的神经精神病学表现密切相关。本研究旨在评估抗P抗体是否可以诱导小鼠异常的脑电活动并研究潜在的细胞病理学机制。方法亲和纯化的人抗核糖体P抗体在血脑屏障（BBB）破坏后经静脉注射入小鼠体内。基于脑电图（EEG）信号对40 Hz点击火车刺激的响应，评估听觉稳态响应（ASSR），该信号是从植入小鼠头骨的电极记录的。免疫荧光染色用于检查海马和皮层神经元和神经胶质的形态和密度。使用TUNEL测定法研究了脑组织中细胞凋亡的存在。PLX3397饮食用于选择性清除小鼠脑部的小胶质细胞。结果循环中的抗P抗体通过破坏BBB引起ASSR的增强和小胶质细胞的活化，而未观察到明显的神经细胞凋亡。相反，当小胶质细胞减少时，抗P抗体会导致ASSR和神经细胞凋亡的严重减少。结论我们的研究表明，抗P抗体可直接诱发大脑中听觉诱发电位的功能障碍，并且小胶质细胞参与了抗P抗体入侵后对神经活动的保护，这可能对NPSLE具有重要意义。PLX3397饮食用于选择性清除小鼠脑部的小胶质细胞。结果循环中的抗P抗体通过破坏BBB引起ASSR的增强和小胶质细胞的活化，而未观察到明显的神经细胞凋亡。相反，当小胶质细胞减少时，抗P抗体会导致ASSR和神经细胞凋亡的严重减少。结论我们的研究表明，抗P抗体可直接诱发大脑中听觉诱发电位的功能障碍，并且小胶质细胞参与了抗P抗体入侵后对神经活动的保护，这可能对NPSLE具有重要意义。PLX3397饮食用于选择性清除小鼠脑部的小胶质细胞。结果循环中的抗P抗体通过破坏BBB引起ASSR的增强和小胶质细胞的活化，而未观察到明显的神经细胞凋亡。相反，当小胶质细胞减少时，抗P抗体会导致ASSR和神经细胞凋亡的严重减少。结论我们的研究表明，抗P抗体可直接诱发大脑中听觉诱发电位的功能障碍，并且小胶质细胞参与了抗P抗体入侵后对神经活动的保护，这可能对NPSLE具有重要意义。结果循环中的抗P抗体通过破坏BBB引起ASSR的增强和小胶质细胞的活化，而未观察到明显的神经细胞凋亡。相反，当小胶质细胞减少时，抗P抗体会导致ASSR和神经细胞凋亡的严重减少。结论我们的研究表明，抗P抗体可直接诱发大脑中听觉诱发电位的功能障碍，并且小胶质细胞参与了抗P抗体入侵后对神经活动的保护，这可能对NPSLE具有重要意义。结果循环中的抗P抗体通过破坏BBB引起ASSR的增强和小胶质细胞的活化，而未观察到明显的神经细胞凋亡。相反，当小胶质细胞减少时，抗P抗体会导致ASSR和神经细胞凋亡的严重减少。结论我们的研究表明，抗P抗体可以直接诱发大脑中听觉诱发电位的功能障碍，并且小胶质细胞参与了抗P抗体入侵后对神经活动的保护，这可能对NPSLE具有重要意义。