1. Academic Validation
  2. Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice

Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice

  • J Neuroinflammation. 2020 Jan 23;17(1):31. doi: 10.1186/s12974-020-1716-9.
Xuejiao Wang 1 Yingzhuo Li 1 Zijie Li 1 Jinhong Li 1 Jingyi Xu 2 Pingting Yang 2 Ling Qin 3
Affiliations

Affiliations

  • 1 Department of Physiology, China Medical University, Shenyang, 110001, People's Republic of China.
  • 2 Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
  • 3 Department of Physiology, China Medical University, Shenyang, 110001, People's Republic of China. lqin@cmu.edu.cn.
Abstract

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.

Keywords

Autoantibody; Electroencephalogram; Encephalopathy; Evoked potentials; Microglia; Phagocytosis.

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