RT Journal Article
T1 Stress-Induced Neuroinflammation: Role of the Toll-Like Receptor-4 Pathway
A1 Gárate, Iciar
A1 García Bueno, Borja
A1 Muñoz Madrigal, José Luis
A1 Caso Fernández, Javier Rubén
A1 Alou Cervera, Luis
A1 Gómez-Lus Centelles, María Luisa
A1 Micó, Juan Antonio
A1 Leza Cerro, Juan Carlos
AB 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.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.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.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.
PB Elsevier
SN 0006-3223
YR 2013
FD 2013-01
LK https://hdl.handle.net/20.500.14352/107061
UL https://hdl.handle.net/20.500.14352/107061
LA eng
NO Gárate I, Garcia-Bueno B, Madrigal JL, Caso JR, Alou L, Gomez-Lus ML, Micó JA, Leza JC. Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway. Biol Psychiatry. 2013 Jan 1;73(1):32-43
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III
NO Centro de Investigación Biomédica en Salud Mental
NO Fundación Santander-UCM
DS Docta Complutense
RD 4 abr 2025