PMID- 28366719 OWN - NLM STAT- MEDLINE DCOM- 20170629 LR - 20201209 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 180 DP - 2017 Jul 1 TI - Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex. PG - 75-82 LID - S0024-3205(17)30117-0 [pii] LID - 10.1016/j.lfs.2017.03.023 [doi] AB - AIMS: Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. MAIN METHODS: BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. KEY FINDINGS: BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. SIGNIFICANCE: We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Li, Shih-Wen AU - Li SW AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Chen, Yu-Chieh AU - Chen YC AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Sheen, Jiunn-Ming AU - Sheen JM AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Hsu, Mei-Hsin AU - Hsu MH AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Tain, You-Lin AU - Tain YL AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chang, Kow-Aung AU - Chang KA AD - Department of Anesthesiolgy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Huang, Li-Tung AU - Huang LT AD - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Traditional Medicine, Chang Gung University, Linkow, Taiwan. Electronic address: huangli@cgmh.org.tw. LA - eng PT - Journal Article DEP - 20170331 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Delayed-Action Preparations) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (NM23 Nucleoside Diphosphate Kinases) RN - 0 (Nerve Tissue Proteins) RN - 0 (collapsin response mediator protein-2) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Bile Ducts/pathology MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/drug effects MH - Chromatography, Liquid MH - Cognition Disorders/*drug therapy/etiology MH - Delayed-Action Preparations MH - Disease Models, Animal MH - Hepatic Encephalopathy/complications/*drug therapy MH - Intercellular Signaling Peptides and Proteins MH - Male MH - Maze Learning/drug effects MH - Minocycline/administration & dosage/*pharmacology MH - NM23 Nucleoside Diphosphate Kinases/genetics MH - Nerve Tissue Proteins/genetics MH - Prefrontal Cortex/*drug effects MH - Proteomics/methods MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Spatial Memory/*drug effects MH - Superoxide Dismutase/metabolism MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Bile duct ligation OT - Cognition OT - Collapsin response mediator protein 2 (CRMP2) OT - Manganese-dependent superoxide dismutase (MnSOD) OT - Minocycline OT - Nucleoside diphosphate kinase B (NME2) OT - Proteomic OT - Spatial memory EDAT- 2017/04/04 06:00 MHDA- 2017/07/01 06:00 CRDT- 2017/04/04 06:00 PHST- 2017/01/04 00:00 [received] PHST- 2017/03/24 00:00 [revised] PHST- 2017/03/29 00:00 [accepted] PHST- 2017/04/04 06:00 [pubmed] PHST- 2017/07/01 06:00 [medline] PHST- 2017/04/04 06:00 [entrez] AID - S0024-3205(17)30117-0 [pii] AID - 10.1016/j.lfs.2017.03.023 [doi] PST - ppublish SO - Life Sci. 2017 Jul 1;180:75-82. doi: 10.1016/j.lfs.2017.03.023. Epub 2017 Mar 31.