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Neurochemical Research

, Volume 43, Issue 1, pp 89–100 | Cite as

Cathepsin C Aggravates Neuroinflammation Involved in Disturbances of Behaviour and Neurochemistry in Acute and Chronic Stress-Induced Murine Model of Depression

  • Yanli Zhang
  • Kai FanEmail author
  • Yanna Liu
  • Gang Liu
  • Xiaohan Yang
  • Jianmei MaEmail author
Original Paper

Abstract

Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0.5 mg/kg) and 6-week unpredictable chronic mild stress (UCMS) exposure to establish acute and chronic stress-induced depression model. We examined and compared the behavioural and proinflammatory cytokine alterations in serum and depression-targeted brain areas of Cat C differentially expressed mice in stress, as well as indoleamine 2,3-dioxygenase (IDO) and 5-hydroxytryptamine (5HT) levels in brain. The results showed that Cat C overexpression (Cat C OE) promoted peripheral and central inflammatory response with significantly increased TNFα, IL-1β and IL-6 in serum, hippocampus and prefrontal cortex, and resultant upregulation of IDO and downregulation of 5HT expression in brain, and thereby aggravated depression-like behaviours accessed by open field test, forced swim test and tail suspension test. In contrast, Cat C knockdown (Cat C KD) partially prevented inflammation, which may help alleviate the symptoms of depression in mice. To the best of our knowledge, we are the first to demonstrate that Cat C aggravates neuroinflammation involved in disturbances of behaviour and neurochemistry in acute and chronic stress-induced murine model of depression.

Keywords

Major depression Cathepsin C Neuroinflammation Behaviour Neurochemistry 

Abbreviations

CNS

Central nervous system

CXCL2

Chemokine (C-X-C motif) ligand 2

FAST

Flexible Accelerated STOP Tetracycline Operator knockin

FST

Forced swim test

5-HT

5-Hydroxytryptamine

Iba-1

Ionized calcium-binding adapter molecule 1

IDO

Indoleamine 2,3-dioxygenase

IHC

Immunohistochemistry

IL-1β

Interleukine-1beta

IL-6

Interleukine-6

LPS

Lipopolysaccharide

LV

Lateral ventricle

OFT

Open field test

PBS

Phosphate buffer saline

PFC

Prefrontal cortex

Plp1

Proteolipid protein 1

TNFα

Tumor necrosis factor alpha

TST

Tail suspension test

UCMS

Unpredictable chronic mild stress

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81271322) and Natural Science Foundation of Liaoning Province (No. 2015020256).

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Dalian Medical UniversityDalianChina

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