PMID- 28791385 OWN - NLM STAT- MEDLINE DCOM- 20180521 LR - 20231213 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 16 IP - 4 DP - 2017 Oct TI - Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress. PG - 4987-4993 LID - 10.3892/mmr.2017.7185 [doi] AB - Accumulating evidence has demonstrated that the sigma-1 receptor (sigma‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that sigma‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of sigma‑1R in PTSD. To address this question, rats were subjected to a single‑prolonged stress (SPS) paradigm and sigma‑1R agonist administration. Open‑field and elevated plus maze tests were implemented to evaluate the effect of sigma‑1R activation on the improvement of anxiety‑like behaviors. Furthermore, the expression levels of BDNF, phosphorylated cAMP responsive element‑binding protein (CREB) and glutamate receptor ionotropic N‑methyl D‑aspartate 2A (NMDAR2A) were investigated in the hippocampi of rats. It was revealed that the downregulation of BDNF, phosphorylated CREB and NMDAR2A induced by SPS were reversed by sigma‑1R activation. Collectively, the results of the present study suggest that the NMDAR2A/CREB/BDNF signaling pathway is involved in the activation of sigma‑1R resulting in therapeutic effects for PTSD. FAU - Ji, Li-Li AU - Ji LL AD - Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China. FAU - Peng, Jun-Bo AU - Peng JB AD - Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China. FAU - Fu, Chang-Hai AU - Fu CH AD - Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China. FAU - Tong, Lei AU - Tong L AD - Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China. FAU - Wang, Zhen-Yu AU - Wang ZY AD - Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China. LA - eng PT - Journal Article DEP - 20170807 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Receptors, sigma) RN - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A) SB - IM MH - Animals MH - Anxiety/*metabolism MH - Behavior Rating Scale MH - Behavior, Animal MH - Biomarkers MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cyclic AMP Response Element-Binding Protein/genetics/*metabolism MH - Disease Models, Animal MH - Gene Expression MH - Hippocampus/metabolism MH - Male MH - Maze Learning MH - Rats MH - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism MH - Receptors, sigma/agonists/*metabolism MH - *Signal Transduction MH - Stress Disorders, Post-Traumatic/metabolism/psychology MH - *Stress, Psychological MH - Sigma-1 Receptor EDAT- 2017/08/10 06:00 MHDA- 2018/05/22 06:00 CRDT- 2017/08/10 06:00 PHST- 2017/01/04 00:00 [received] PHST- 2017/07/11 00:00 [accepted] PHST- 2017/08/10 06:00 [pubmed] PHST- 2018/05/22 06:00 [medline] PHST- 2017/08/10 06:00 [entrez] AID - 10.3892/mmr.2017.7185 [doi] PST - ppublish SO - Mol Med Rep. 2017 Oct;16(4):4987-4993. doi: 10.3892/mmr.2017.7185. Epub 2017 Aug 7.