Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex

Shih Wen Li, Yu Chieh Chen, Jiunn Ming Sheen, Mei Hsin Hsu, You Lin Tain, Kow Aung Chang, Li Tung Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalLife Sciences
Volume180
DOIs
StatePublished - 01 07 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

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

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