PMID- 28806788 OWN - NLM STAT- MEDLINE DCOM- 20171009 LR - 20181202 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 8 DP - 2017 TI - Chronic unpredictable stress exacerbates surgery-induced sickness behavior and neuroinflammatory responses via glucocorticoids secretion in adult rats. PG - e0183077 LID - 10.1371/journal.pone.0183077 [doi] LID - e0183077 AB - METHODS: Sprague-Dawley adult male rats (12-14 weeks old) were exposed to 14-day CUS and then subjected to partial hepatectomy 24 h after the last stress session. The rats were pretreated with an antagonist of the glucocorticoids (GCs) receptor RU486 (30 mg/kg, i.p.) 1 h prior to stress exposure. The behavioral changes were evaluated with open field test and elevated plus-maze test. The hippocampal cytokines interleukin (IL)-1beta and IL-6 were measured on postoperative days 1, 3 and 7. Ionized calcium binding adaptor protein (Iba)-1, microglial M2 phenotype marker Arg1, brain derived neurotrophic factor (BDNF) and CD200 were also examined at each time point. RESULTS: CUS exacerbated surgery-induced sickness behavior. Exposure to CUS alone failed to alter the levels of pro-inflammatory cytokines in the brain. However, CUS exaggerated surgery-induced pro-inflammatory cytokines expression (e.g. IL-1beta and IL-6) and upregulated the levels of Iba-1 on postoperative days 1 and 3. An additional significant decreased BDNF, CD200 and a lower level of Arg1 were also observed in the stressed rats following surgical procedure. Pretreatment with RU486 blunted the potentiating effects of CUS on surgery-induced sickness behavior and neuroinflammatory responses. CONCLUSION: Chronic unpredictable stress enhanced surgery-induced sickness behavior and neuroinflammatory responses. Stress-induced GCs played a pivotal role in enhancing surgery-induced neuroinflammatory processes by modulation of microglia functions. FAU - Wang, Na AU - Wang N AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Ma, Hong AU - Ma H AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Li, Zhe AU - Li Z AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Gao, Yalei AU - Gao Y AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Cao, Xuezhao AU - Cao X AUID- ORCID: 0000-0003-4824-6934 AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Jiang, Yanhua AU - Jiang Y AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Zhou, Yongjian AU - Zhou Y AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. FAU - Liu, Sidan AU - Liu S AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning, China. LA - eng PT - Journal Article DEP - 20170814 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Aif1 protein, rat) RN - 0 (Antigens, CD) RN - 0 (Biomarkers) RN - 0 (Calcium-Binding Proteins) RN - 0 (Glucocorticoids) RN - 0 (Interleukin-6) RN - 0 (Microfilament Proteins) RN - 0 (RNA, Messenger) RN - EC 3.5.3.1 (Arginase) RN - UQ4V77A8VA (antigens, CD200) SB - IM MH - Animals MH - Antigens, CD/genetics/metabolism MH - Anxiety/blood/complications/physiopathology MH - Arginase/metabolism MH - Biomarkers/metabolism MH - Body Weight MH - Calcium-Binding Proteins/metabolism MH - Chronic Disease MH - Glucocorticoids/blood/*metabolism MH - Hepatectomy/*adverse effects MH - Hippocampus/pathology/physiopathology MH - *Illness Behavior MH - Inflammation/blood/*complications/pathology/physiopathology MH - Interleukin-6/metabolism MH - Male MH - Microfilament Proteins/metabolism MH - Microglia/metabolism MH - Motor Activity MH - Neurons/*pathology MH - Phenotype MH - RNA, Messenger/genetics/metabolism MH - Rats, Sprague-Dawley MH - Stress, Psychological/blood/*complications/physiopathology MH - Up-Regulation PMC - PMC5555668 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/08/15 06:00 MHDA- 2017/10/11 06:00 PMCR- 2017/08/14 CRDT- 2017/08/15 06:00 PHST- 2017/01/17 00:00 [received] PHST- 2017/07/28 00:00 [accepted] PHST- 2017/08/15 06:00 [entrez] PHST- 2017/08/15 06:00 [pubmed] PHST- 2017/10/11 06:00 [medline] PHST- 2017/08/14 00:00 [pmc-release] AID - PONE-D-17-02136 [pii] AID - 10.1371/journal.pone.0183077 [doi] PST - epublish SO - PLoS One. 2017 Aug 14;12(8):e0183077. doi: 10.1371/journal.pone.0183077. eCollection 2017.