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 [F] Diseases Research  / PubMed Research Articles  /
Cathepsin C Aggravates Neuroinflammation Involved in Disturbances of Behaviour and Neurochemistry in Acute and Chronic Stress-Induced Murine Model of Depression.




Neurochemical research 2017 Jun 17; ()


Zhang Y1; Fan K2; Liu Y3; Liu G4; Yang X5; Ma J6;

Author Information
  • 1Dalian Medical University, Dalian, Liaoning, China.
  • 2Dalian Medical University, Dalian, Liaoning, China. 2286130554@qq.com.
  • 3Dalian Medical University, Dalian, Liaoning, China.
  • 4Dalian Medical University, Dalian, Liaoning, China.
  • 5Dalian Medical University, Dalian, Liaoning, China.
  • 6Dalian Medical University, Dalian, Liaoning, China. ma_jianmei@hotmail.com.


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.




Publication Type: Journal Article

This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.

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