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  Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia.

Couch, I., Anthony, D. C., Dolgov, O., Rewischin, A., Festoff, B., Santos, A. I., et al. (2013). Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain, Behavior and Immunity, 29, 136-146. doi:10.1016/j.bbi.2012.12.017.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F5E1-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-7218-E
Genre: Journal Article

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 Creators:
Couch, I., Author
Anthony, D. C., Author
Dolgov, O.1, Author              
Rewischin, A., Author
Festoff, B., Author
Santos, A. I., Author
Steinbusch, H. W., Author
Strekalova, T., Author
Affiliations:
1Department of Molecular Cell Biology, MPI for biophysical chemistry, Max Planck Society, ou_578585              

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Free keywords: Chronic stress; Anhedonia; TNF; SERT; 5-HT2A
 Abstract: A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference < 65%) or resilience (sucrose preference > 65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2, 3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of lba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression.

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Language(s): eng - English
 Dates: 2013-01-072013-03
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.bbi.2012.12.017
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Title: Brain, Behavior and Immunity
Source Genre: Journal
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Pages: - Volume / Issue: 29 Sequence Number: - Start / End Page: 136 - 146 Identifier: -