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

Authors Li C, Xu X, Zhang X, Cheng K, Guo Y, Jie J, Guo H, He Y, Zhou C, Gui S, Zhong X, Wang H, Xie P

Received 5 June 2018

Accepted for publication 17 September 2018

Published 15 November 2018 Volume 2018:14 Pages 3121—3132

DOI https://doi.org/10.2147/NDT.S176399

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Yu-Ping Ning


Chenmeng Li,1–3,* Xiaoyan Xu,2–4,* Xiong Zhang,2–4,* Ke Cheng,2,3,* Yujie Guo,1–3 Jie Jie,1–3 Hua Guo,1–3 Yong He,1–3 Chanjuan Zhou,2,3 Siwen Gui,2,3 Xiaogang Zhong,2,3 Haiyang Wang,2–4 Peng Xie1–4

1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; 2Department of Neurology Institute of Neuroscience and Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; 3Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; 4Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

*These authors contributed equally to this work

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: Borna disease virus, ERK/CREB/BDNF signaling pathway, neonatal Borna disease

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