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Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway.
- Source :
-
Biological psychiatry [Biol Psychiatry] 2013 Jan 01; Vol. 73 (1), pp. 32-43. Date of Electronic Publication: 2012 Aug 18. - Publication Year :
- 2013
-
Abstract
- Background: Stressful challenges are associated with variations in immune parameters, including increased innate immunity/inflammation. Among possible mechanisms through which brain monitors peripheral immune responses, toll-like receptors (TLRs) recently emerged as the first line of defense against invading microorganisms. Their expression is modulated in response to pathogens and other environmental stresses.<br />Methods: Taking into account this background, the present study aimed to elucidate whether the toll-like receptor-4 (TLR-4) signaling pathway is activated after repeated restraint/acoustic stress exposure in mice prefrontal cortex (PFC), the potential regulatory mechanism implicated (i.e., bacterial translocation), and its role in conditions of stress-induced neuroinflammation, using a genetic strategy: C3H/HeJ mice with a defective response to lipopolysaccharide stimulation of TLR-4.<br />Results: Stress exposure upregulates TLR-4 pathway in mice PFC. Stress-induced inflammatory nuclear factor κB activation, upregulation of the proinflammatory enzymes nitric oxide synthase and cyclooxygenase type 2, and cellular oxidative/nitrosative damage are reduced when the TLR-4 pathway is defective. Conversely, TLR-4 deficient mice presented higher levels of the anti-inflammatory nuclear factor peroxisome proliferator activated receptor-gamma after stress exposure than control mice. The series of experiments using antibiotic intestinal decontamination also suggest a role for bacterial translocation on TLR-4 activation in PFC after stress exposure.<br />Conclusions: Taken together, all the data presented here suggest a bifunctional role of TLR-4 signaling pathway after stress exposure by triggering neuroinflammation at PFC level and regulating gut barrier function/permeability. Furthermore, our data suggest a possible protective role of antibiotic decontamination in stress-related pathologies presenting increased intestinal permeability (leaky gut) such as depression, showing a potential therapeutic target that deserves further consideration.<br /> (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Acute-Phase Proteins metabolism
Animals
Bacterial Translocation drug effects
Bacterial Translocation physiology
Carrier Proteins metabolism
Colon metabolism
Immunoglobulin A metabolism
Inflammation blood
Inflammation complications
Inflammation Mediators metabolism
Lipopolysaccharides metabolism
Male
Membrane Glycoproteins metabolism
Mice
Mice, Inbred C3H
Prefrontal Cortex metabolism
Signal Transduction physiology
Stress, Psychological blood
Stress, Psychological complications
Stress, Psychological metabolism
Toll-Like Receptor 4 metabolism
Inflammation metabolism
Stress, Psychological physiopathology
Toll-Like Receptor 4 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2402
- Volume :
- 73
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biological psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 22906518
- Full Text :
- https://doi.org/10.1016/j.biopsych.2012.07.005