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Original Research

Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats

Chenmeng Li1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Xiaoyan Xu2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected];4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China, [email protected]

Xiong Zhang2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected];4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China, [email protected]

Ke Cheng2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Yujie Guo1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Jie Jie1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Hua Guo1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Yong He1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Chanjuan Zhou2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Siwen Gui2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Xiaogang Zhong2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected]

Haiyang Wang2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected];4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China, [email protected]

Peng Xie1 Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China, [email protected];2 Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China, [email protected];3 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China, [email protected];4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China, [email protected]Correspondence[email protected]

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Abstract

Background

Neuropsychiatric disorders are devastating illnesses worldwide; however, the potential involvement of viruses in the pathophysiological mechanisms of psychiatric diseases have not been clearly elucidated. Borna disease virus (BDV) is a neurotropic, noncytopathic RNA virus.

Materials and methods

In this study, we infected neonatal rats intracranially with BDV Hu-H1 and Strain V within 24 hours of birth. Psychological phenotypes were assessed using sucrose preference test, open field test, elevated plus maze test, and forced swim test. The protein expression of ERK/CREB/BDNF pathway was assessed by Western blotting of in vitro and in vivo samples.

Results

Hu-H1-infected rats showed anxiety-like behavior 8 weeks postinfection while Strain V-infected rats demonstrated a certain abnormal behavior. Phosphorylated ERK1/2 was significantly upregulated in the hippocampi of Strain V- and Hu-H1-infected rats compared with control rats, indicating that Raf/MEK/ERK signaling was activated.

Conclusion

The data suggested that infection of neonatal rats with BDV Hu-H1 and Strain V caused behavioral abnormalities that shared common molecular pathways, providing preliminary evidences to investigate the underlying mechanisms of psychiatric disorders caused by BDV.

Keywords:

Acknowledgments

This study was financially supported by the National Key Research and Development Program of China (Grant No 2017YFA0505700), the Young Project of National Natural Science Foundation of China (Grant No 81601207), the Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No KJ1600223), and the Basic and Frontier Exploration Project of Chongqing (Grant No CSTC2016JCYJA0159 and Grant No CSTC2015JCYJA10081). We thank Dr Jian Lu for his assistance with graphics. We thank Liwen Bianji, Edanz Editing, China, for editing the English text of the draft of this manuscript.

Disclosure

The authors report no conflicts of interest in this work.

Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats

Background

Materials and methods

Results

Conclusion

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Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats

Abstract

Background

Materials and methods

Results

Conclusion

Acknowledgments

Disclosure

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