Psychopharmacology

, Volume 235, Issue 1, pp 179–191 | Cite as

Chronic N-acetylcysteine treatment alleviates acute lipopolysaccharide-induced working memory deficit through upregulating caveolin-1 and synaptophysin in mice

  • Xianzhi Shen
  • Yanyun Sun
  • Mengwei Wang
  • Hui Shu
  • Li-Juan Zhu
  • Pei-Yun Yan
  • Jun-Fang Zhang
  • Xinchun Jin
Original Investigation

Abstract

Rationale

Working memory (WM) is a dynamic encoding process and an active representation of information over a short time. The ability to guide forthcoming behavior would be disrupted if WM was impaired by various factors including inflammation, stress, free radicals, and disease states such as schizophrenia. However, the mechanism underlying acute working memory impairment remains to be defined.

Objectives

In this study, we tested the hypothesis that decreased caveolin-1 (Cav-1) and synaptophysin (SYP) accounted for the WM impairment challenged with acute intraperitoneally lipopolysaccharide (LPS), which mimicked neuroinflammation. Delayed alternation T-maze task (DAT) was used to assess working memory of adult male C57BL/6 mice, and western blot and immunostaining were used to detect protein expression and distribution in medial prefrontal cortex (mPFC) and hippocampus.

Results

Our results showed that LPS dose-dependently induced working memory deficit accompanied by the decrease of Cav-1 and SYP in mPFC but not hippocampus. In addition, LPS significantly decreased protein level of Cav-1 and SYP in neurons by activating microglia cells. More important, 2-week N-acetylcysteine (NAC) treatment dose-dependently inhibited LPS-induced working memory deficit by improving the ability to use Lose-shift but not Win-shift strategy and significantly inhibited LPS-induced downregulation of Cav-1 and SYP in mPFC.

Conclusions

Taken together, our findings demonstrate that chronic NAC treatment alleviates acute LPS-induced working memory deficit through upregulating Cav-1 and SYP in mice.

Keywords

N-acetylcysteine Lipopolysaccharide Working memory Caveolin-1 Synaptophysin Mice 

Abbreviations

BDL

Bile duct ligation;

Cav-1

Caveolin-1

DAT

Delayed alternation T-maze task

IL-1β

Interleukine-1 beta

i.p.

Intraperitoneally

LCM

LPS-conditioned medium

LPS

lipopolysaccharide

mPFC

Medial prefrontal cortex

NAC

N-acetylcysteine

ROS

Reactive oxygen series

SYP

Synaptophysin

TNF-α

Tumor necrosis factor-α

WM

Working memory

Notes

Author contributions

This work was performed and accomplished by all authors. XS, YS, MW, HS, LJZ, and PY contributed to the execution of the entire research project and the statistical analyses. XS, JZ, and XJ wrote the manuscript. All authors have read and approved the final manuscript.

Compliance with ethical standards

All experimental procedures were approved by the University Committee on Animal Care of Soochow University and performed according to the NIH Guide for the Care and Use of Laboratory Animals.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Xianzhi Shen
    • 1
    • 2
  • Yanyun Sun
    • 1
  • Mengwei Wang
    • 1
  • Hui Shu
    • 1
  • Li-Juan Zhu
    • 1
  • Pei-Yun Yan
    • 3
  • Jun-Fang Zhang
    • 3
    • 4
  • Xinchun Jin
    • 1
    • 2
  1. 1.Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of NeuroscienceThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of EducationYantai UniversityYantaiChina
  3. 3.School of MedicineNingbo UniversityNingboChina
  4. 4.Zhejiang Provincial Key Laboratory of PathophysiologyNingboChina

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