Proteomic Analysis of Rhesus Macaque Brain Explants Treated With Borrelia burgdorferi Identifies Host GAP-43 as a Potential Factor Associated With Lyme Neuroborreliosis

用伯氏疏螺旋体治疗的恒河猴脑外植体的蛋白质组学分析表明宿主 GAP-43 是与莱姆神经性疏螺旋体病相关的潜在因素

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作者:Lianbao Li, Lisha Luo, Taigui Chen, Wenjing Cao, Xin Xu, Yu Zhang, Peng Yue, Yuxin Fan, Jingjing Chen, Meixiao Liu, Mingbiao Ma, Lvyan Tao, Yun Peng, Yan Dong, Bingxue Li, Suyi Luo, Jing Kong, Guozhong Zhou, Shiyuan Wen, Aihua Liu, Fukai Bao

Background

Lyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.

Conclusions

Elevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment.

Methods

Cultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened.

Results

We identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively. Conclusions: Elevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment.

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