Revision to psychopharmacology mRNA and microRNA profiles are associated with stress susceptibility and resilience induc

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ORIGINAL INVESTIGATION

Revision to psychopharmacology mRNA and microRNA profiles are associated with stress susceptibility and resilience induced by psychological stress in the prefrontal cortex Jiuyong Yang 1 & Jinyan Sun 1 & Yanjun Lu 1 & Tingting An 1 & Wei Lu 1 & Jin-Hui Wang 1,2,3 Received: 27 February 2020 / Accepted: 12 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Objectives The prefrontal cortex is associated with many mental neurological diseases. The mRNA and microRNA profiles of stress susceptibility and resilience induced by psychological stress in the prefrontal cortex remain to be elucidated. Methods The C57 observer was placed in the cage next to the CD1 mouse and suffered psychological stress by watching the CD1 attacking another C57 mouse. After 5 days of psychological stress, the degree of fear memory and anxiety of mice were measured by social interaction test and elevated plus maze (EPM). The prefrontal cortex was extracted and mRNA and microRNA profiles were analyzed by high-throughput sequencing. Results In susceptible mice versus resilient mice, the downregulation of genes involved in serotonergic synapse may be related to the susceptibility to psychological stress. The imbalanced regulation of genes involved in VEGF, p53, chemokine, Ras, sphingolipid, GnRH, MAPK, and NOD-like receptor signaling pathways may be related to the susceptibility to psychological stress. Compared with control mice, susceptible mice and resilient mice have changed genes involved in serotonergic synapse, neuroactive ligand-receptor interaction, axon guidance, calcium, cAMP, GnRH, estrogen, PI3K-Akt, MAPK, Rap1, and Ras signaling pathways, these changes may be related to psychological stress processing. The sequencing results of mRNAs and microRNAs were verified by qRT-PCR and dual-luciferase reporter assay. Conclusions The downregulation of genes involved in serotonergic synapse and imbalance of signaling pathways in the prefrontal cortex may be related to susceptibility to psychological stress. Keywords Psychological stress . Susceptibility . Resilience . Anxiety and prefrontal cortex

Introduction There are many types of stress, including acute severe stress and chronic mild stress, psychological stress, and physical Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05593-x) contains supplementary material, which is available to authorized users. * Wei Lu [email protected] * Jin-Hui Wang [email protected] 1

School of Pharmacy, Qingdao University, 38 Dengzhou, Qingdao 266021, Shandong, China

2

University of Chinese Academy of Sciences, Beijing 100049, China

3

Institute of Biophysics, University of Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China

stress, and excessive stress can induce phobia, anxiety, depression, and post-traumatic stress disorder (PTSD) (Coutellier and Usdin 2011; Desmedt et al. 2015; Orsini and Maren 2012; Si et al. 2018). People’s responses to stress and trauma vary wid

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