Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats
Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats
复制标题
DOI：
10.2147/ndt.s176399
复制
发表时间：
2018-11
影响因子：
3.2
通讯作者：
Chenmeng Li;Xiaoyan Xu;Xiong Zhang;K. Cheng;Yujie Guo;Jie Jie-Jie;Hua Guo;Yong He;Chanjuan Zhou;Siwen Gui;Xiaogang Zhong;Haiyang Wang;P. Xie
中科院分区：
文献类型：
--
作者：
Chenmeng Li;Xiaoyan Xu;Xiong Zhang;K. Cheng;Yujie Guo;Jie Jie-Jie;Hua Guo;Yong He;Chanjuan Zhou;Siwen Gui;Xiaogang Zhong;Haiyang Wang;P. Xie
背景神经精神障碍在世界范围内是一种毁灭性的疾病；然而，病毒在精神疾病的病理生理机制中的潜在参与尚不清楚。博尔纳病病毒(BDV)是一种嗜神经、非细胞病变的RNA病毒。材料与方法在新生大鼠出生后24小时内，用BDV Hu-H1株和V株对新生大鼠进行脑内感染。采用蔗糖偏爱试验、旷场试验、高架迷宫试验和强迫游泳试验评定心理表型。用Western blotting检测ERK/CREB/BDNF通路在体外和体内的蛋白表达。结果HU-H1感染组大鼠在感染后8周出现焦虑样行为，而V株感染组大鼠表现出一定的异常行为。与对照组相比，V株和Hu-H1感染组大鼠海马区磷酸化ERK1/2表达显著上调，表明Raf/MEK/ERK信号通路被激活。结论BDV Hu-H1株和V株感染新生大鼠可引起行为异常，具有共同的分子机制，为探讨BDV引起精神障碍的潜在机制提供了初步依据。
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.