title: Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Shih-Wen
authors.initials: SW
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Jiunn-Ming
authors.initials: JM
authors.lastname: Sheen
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mei-Hsin
authors.initials: MH
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Department of Anesthesiolgy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kow-Aung
authors.initials: KA
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000473:pathology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects; D002853:Chromatography, Liquid; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000150:complications / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D017397:Prefrontal Cortex / Q000187:drug effects*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D065852:Spatial Memory / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003692:Delayed-Action Preparations; D036341:Intercellular Signaling Peptides and Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D013482:Superoxide Dismutase; D008911:Minocycline
keywords: Bile duct ligation; Cognition; Collapsin response mediator protein 2 (CRMP2); Manganese-dependent superoxide dismutase (MnSOD); Minocycline; Nucleoside diphosphate kinase B (NME2); Proteomic; Spatial memory