Anti-CRMP2 antibody induces anxiety-like behavior and increases pyramidal neuron excitability in mice

抗 CRMP2 抗体诱导小鼠焦虑样行为并增加锥体神经元兴奋性

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作者:Yue Pan, Yawei Jiang, Dongmei Wang, Zhipeng Guo, Fenfen He, Zirui Chen, Chaowei Dai, Zhirong Yuan, Rongqing Chen, Kaibiao Xu, Yafang Hu

Background

We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab.

Conclusion

In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab.

Methods

Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes.

Results

The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected.

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