PMID- 29373817 OWN - NLM STAT- MEDLINE DCOM- 20181113 LR - 20181202 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 133 DP - 2018 May 1 TI - trans-Resveratrol ameliorates anxiety-like behaviors and fear memory deficits in a rat model of post-traumatic stress disorder. PG - 181-188 LID - S0028-3908(17)30632-9 [pii] LID - 10.1016/j.neuropharm.2017.12.035 [doi] AB - trans-Resveratrol, a natural polyphenol enriched in grape seed and skin, has been extensively investigated for its antioxidant, anti-inflammatory and anti-psychiatric properties. The present study examined the effects of trans-resveratrol on ameliorating anxiety-like behaviors and fear memory deficits induced by time-dependent sensitization (TDS) procedure, which is a classical animal model for mimicking posttraumatic stress disorder (PTSD). The results suggested that trans-resveratrol at doses of 10, 20 and 40 mg/kg (via gavage, i.g.) reversed TDS-induced decreases in the percentage of time spent in the center of arena, the open arm entries and time spent in the open arms in the open field and elevated plus maze tests. It also decreased the percentage of freezing time in the contextual fear paradigm that was increased in TDS treated rats. Further study suggested that TDS-induced abnormality in the limbic hypothalamus-pituitary-adrenal gland (L-HPA) axis was reversed by trans-resveratrol, i.e. it reversed increased adrenal gland index and corticotropin-releasing factor (CRF) levels, and rescued the differential expression of glucocorticoid receptor (GR) in the hypothalamus, hippocampus and amygdala. Neurobiological studies suggested that trans-resveratrol increased phosphorylation of cAMP response element binding protein (pCREB) and brain derived neurotrophic factor (BDNF) levels, which were decreased in rats subjected to TDS. These results provide compelling evidence that trans-resveratrol protects neurons against PTSD-like stress insults by regulation of L-HPA axis function and activation of downstream neuroprotective molecules, such as pCREB and BDNF expression. CI - Published by Elsevier Ltd. FAU - Li, Gaowen AU - Li G AD - Ningbo College of Health Sciences, Ningbo, Zhejiang Province 425100, China. FAU - Wang, Gang AU - Wang G AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, The Affiliated Hospital of Nanjing Medical University, Hangzhou, Zhejiang Province 310006, China. FAU - Shi, Jing AU - Shi J AD - School of Pharmacy and Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang Province 310053, China. FAU - Xie, Xueyi AU - Xie X AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214, USA; College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. FAU - Fei, Ning AU - Fei N AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province 325021, China. FAU - Chen, Ling AU - Chen L AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, The Affiliated Hospital of Nanjing Medical University, Hangzhou, Zhejiang Province 310006, China. FAU - Liu, Na AU - Liu N AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214, USA. FAU - Yang, Mingxin AU - Yang M AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214, USA. FAU - Pan, Jianchun AU - Pan J AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province 325021, China. FAU - Huang, Wu AU - Huang W AD - Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213161, China. Electronic address: wuhuang_czey@163.com. FAU - Xu, Ying AU - Xu Y AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214, USA. Electronic address: yxu9@buffalo.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180131 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Stilbenes) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - Q369O8926L (Resveratrol) SB - IM MH - Adrenal Glands/drug effects/pathology MH - Analysis of Variance MH - Animals MH - Antioxidants/*therapeutic use MH - Anxiety/*drug therapy/etiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - CREB-Binding Protein/metabolism MH - Corticotropin-Releasing Hormone/metabolism MH - Disease Models, Animal MH - Exploratory Behavior/drug effects MH - Fear/*drug effects MH - Male MH - Maze Learning/drug effects MH - Memory Disorders/*drug therapy/etiology MH - Rats MH - Rats, Sprague-Dawley MH - Resveratrol MH - Stilbenes/*therapeutic use MH - Stress Disorders, Post-Traumatic/complications/pathology OTO - NOTNLM OT - Anxiety OT - Limbic hypothalamus-pituitary-adrenal axis (L-HPA) OT - Post-traumatic stress disorder (PTSD) OT - Time-dependent sensitization (TDS) procedure OT - trans-Resveratrol EDAT- 2018/01/27 06:00 MHDA- 2018/11/14 06:00 CRDT- 2018/01/27 06:00 PHST- 2017/10/12 00:00 [received] PHST- 2017/12/04 00:00 [revised] PHST- 2017/12/19 00:00 [accepted] PHST- 2018/01/27 06:00 [pubmed] PHST- 2018/11/14 06:00 [medline] PHST- 2018/01/27 06:00 [entrez] AID - S0028-3908(17)30632-9 [pii] AID - 10.1016/j.neuropharm.2017.12.035 [doi] PST - ppublish SO - Neuropharmacology. 2018 May 1;133:181-188. doi: 10.1016/j.neuropharm.2017.12.035. Epub 2018 Jan 31.