PMID- 30086367 OWN - NLM STAT- MEDLINE DCOM- 20190329 LR - 20211204 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 388 DP - 2018 Sep 15 TI - Sulforaphane Alleviates Lipopolysaccharide-induced Spatial Learning and Memory Dysfunction in Mice: The Role of BDNF-mTOR Signaling Pathway. PG - 357-366 LID - S0306-4522(18)30536-0 [pii] LID - 10.1016/j.neuroscience.2018.07.052 [doi] AB - Peripheral immune activation could cause neuroinflammation, leading to a series of central nervous system (CNS) disorders, such as spatial learning and memory dysfunction. However, its pathogenic mechanism and therapeutic strategies are not yet determined. The present study aimed to investigate the therapeutic effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced spatial learning and memory dysfunction, and tried to elucidate its relationship with the role of hippocampal brain-derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling pathway. Intraperitoneal injection of LPS for consecutive 7 days to mice caused abnormal behaviors in Morris water maze test (MWMT), while systemic administration of SFN notably reversed the abnormal behaviors. In addition, hippocampal levels of inflammatory cytokines, synaptic proteins, BDNF-tropomyosin receptor kinase B (TrkB) and mTOR signaling pathways were altered in the processes of LPS-induced cognitive dysfunction and SFN's therapeutic effects. Furthermore, we found that ANA-12 (a TrkB inhibitor) or rapamycin (a mTOR inhibitor) could block the beneficial effects of SFN on LPS-induced cognitive dysfunction, and that hippocampal levels of synaptic proteins, BDNF-TrkB and mTOR signaling pathways were also notably changed. In conclusion, the results of the present study suggest that SFN could elicit improving effects on LPS-induced spatial learning and memory dysfunction, which is likely related to the regulation of hippocampal BDNF-mTOR signaling pathway. CI - Copyright (c) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Gao, Jie AU - Gao J AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xiong, Bingrui AU - Xiong B AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Bo AU - Zhang B AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Shan AU - Li S AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Huang, Niannian AU - Huang N AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhan, Gaofeng AU - Zhan G AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Jiang, Riyue AU - Jiang R AD - Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Yang, Ling AU - Yang L AD - Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Wu, Yeshun AU - Wu Y AD - Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Miao, Liying AU - Miao L AD - Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Zhu, Bin AU - Zhu B AD - Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China. FAU - Yang, Chun AU - Yang C AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: chunyang@tjh.tjmu.edu.cn. FAU - Luo, Ailin AU - Luo A AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: alluo@tjh.tjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180804 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Isothiocyanates) RN - 0 (Lipopolysaccharides) RN - 0 (Nootropic Agents) RN - 0 (Sulfoxides) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GA49J4310U (sulforaphane) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Hippocampus/drug effects/immunology MH - Inflammation/complications/*drug therapy/psychology MH - Isothiocyanates/*pharmacology MH - Learning Disabilities/*drug therapy/etiology/immunology MH - Lipopolysaccharides MH - Male MH - Maze Learning/drug effects/physiology MH - Memory Disorders/*drug therapy/etiology/immunology MH - Mice, Inbred C57BL MH - Nootropic Agents/*pharmacology MH - Signal Transduction/drug effects MH - Spatial Memory/drug effects/physiology MH - Sulfoxides MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - brain-derived neurotrophic factor OT - lipopolysaccharide OT - mammalian target of rapamycin OT - spatial learning and memory dysfunction OT - sulforaphane EDAT- 2018/08/08 06:00 MHDA- 2019/03/30 06:00 CRDT- 2018/08/08 06:00 PHST- 2018/06/01 00:00 [received] PHST- 2018/07/29 00:00 [revised] PHST- 2018/07/30 00:00 [accepted] PHST- 2018/08/08 06:00 [pubmed] PHST- 2019/03/30 06:00 [medline] PHST- 2018/08/08 06:00 [entrez] AID - S0306-4522(18)30536-0 [pii] AID - 10.1016/j.neuroscience.2018.07.052 [doi] PST - ppublish SO - Neuroscience. 2018 Sep 15;388:357-366. doi: 10.1016/j.neuroscience.2018.07.052. Epub 2018 Aug 4.