PMID- 32006528 OWN - NLM STAT- MEDLINE DCOM- 20200323 LR - 20200323 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 245 DP - 2020 Mar 15 TI - Inhibition of steroid receptor coactivator-1 in the hippocampus impairs the consolidation and reconsolidation of contextual fear memory in mice. PG - 117386 LID - S0024-3205(20)30133-8 [pii] LID - 10.1016/j.lfs.2020.117386 [doi] AB - AIMS: Steroid receptor coactivator-1 (SRC-1) is a key coactivator for the efficient transcriptional activity of steroids in the regulation of hippocampal functions. However, the effect of SRC-1 on hippocampal memory processes remains unknown. Our aim was to investigate the roles of hippocampal SRC-1 in the consolidation and reconsolidation of contextual fear memory in mice. MAIN METHODS: Contextual fear conditioning paradigm was constructed in adult male C57BL/6 mice to examine the fear learning and memory processes. Adeno-associated virus (AAV) vector-mediated RNA interference (RNAi) was infused into hippocampus to block hippocampal SRC-1 level. Immunofluorescent staining was used to detect the efficiency of transfection. High plus maze and open field test were used to determine anxiety and locomotor activity. Western blot analyses were used to detect the expression of SRC-1 and synaptic proteins in the hippocampus. KEY FINDINGS: We first showed that the expression of SRC-1 was regulated by fear conditioning training in a time-dependent manner, and knockdown of SRC-1 impaired contextual fear memory consolidation without affecting innate anxiety or locomotor activity. In addition, hippocampal SRC-1 was also regulated by the retrieval of contextual fear memory, and downregulation of SRC-1 disrupted fear memory reconsolidation. Moreover, knockdown of SRC-1 reversed the increased GluR1 and PSD-95 levels induced by contextual fear memory retrieval. SIGNIFICANCE: Our data indicate that hippocampal SRC-1 is required for the consolidation and reconsolidation of contextual fear memory, and SRC-1 may be a potential therapeutic target for mental disorders that are involved in hippocampal memory dysfunction. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Chen, Xiuxiu AU - Chen X AD - Department of Military Psychology, College of Psychology, Army Medical University, Chongqing 400038, China. FAU - Tian, Yiqin AU - Tian Y AD - Department of Military Psychology, College of Psychology, Army Medical University, Chongqing 400038, China. FAU - Zhu, Haitao AU - Zhu H AD - Department of Neurology, Airborne Military Hospital, Chinese People's Liberation Army, Wuhan 430014, China. FAU - Bian, Chen AU - Bian C AD - Department of Military Psychology, College of Psychology, Army Medical University, Chongqing 400038, China; Department of Developmental Psychology of Army man, College of Psychology, Army Medical University, Chongqing 400038, China. Electronic address: bc818@163.com. FAU - Li, Min AU - Li M AD - Department of Military Psychology, College of Psychology, Army Medical University, Chongqing 400038, China. Electronic address: limin52267@tmmu.edu.cn. LA - eng PT - Journal Article DEP - 20200130 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - EC 2.3.1.48 (Ncoa1 protein, mouse) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - Animals MH - Blotting, Western MH - Conditioning, Classical/drug effects/physiology MH - Fear/*drug effects/physiology/psychology MH - Fluorescent Antibody Technique MH - Hippocampus/*drug effects/physiology MH - Male MH - Maze Learning/drug effects/physiology MH - Memory/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Nuclear Receptor Coactivator 1/*antagonists & inhibitors/physiology OTO - NOTNLM OT - Consolidation OT - Contextual fear memory OT - Hippocampus OT - Reconsolidation OT - Steroid receptor coactivator-1 COIS- Declaration of competing interest The authors declare that they have no conflicts of interest. EDAT- 2020/02/02 06:00 MHDA- 2020/03/24 06:00 CRDT- 2020/02/02 06:00 PHST- 2019/09/23 00:00 [received] PHST- 2020/01/20 00:00 [revised] PHST- 2020/01/28 00:00 [accepted] PHST- 2020/02/02 06:00 [pubmed] PHST- 2020/03/24 06:00 [medline] PHST- 2020/02/02 06:00 [entrez] AID - S0024-3205(20)30133-8 [pii] AID - 10.1016/j.lfs.2020.117386 [doi] PST - ppublish SO - Life Sci. 2020 Mar 15;245:117386. doi: 10.1016/j.lfs.2020.117386. Epub 2020 Jan 30.