Effects of LPS-induced immune activation prior to trauma exposure on PTSD-like symptoms in mice.
The prevalence of posttraumatic stress disorder (PTSD) is high in the armed services, with a rate up to 20%. Multiple studies have associated markers of inflammatory signaling prior to trauma with increased risk of PTSD, suggesting a potential role of the immune system in the development of this psychiatric disorder. One question that arises is if "priming" the immune system before acute trauma alters the stress response and increases enduring effects of trauma. We investigated the time course of inflammatory response to predator stress, a robust stressor that induces enduring PTSD-like behaviors, and the modulation of these effects via prior immune activation with the bacterial endotoxin, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist. Mice exposed to predator stress exhibited decreased pro-/anti-inflammatory balance in the brain 6h after stress, suggesting that predator exposure acutely suppressed the immune system by increasing anti-inflammatory cytokines levels. Acute immune activation with LPS before a single predator stress did not alter the enduring avoidance behavior in stressed mice. Our findings suggest that acute inflammation, at least via TLR4 activation, is not sufficient to increase susceptibility for PTSD-like behaviors in this model. Future studies will examine if chronic inflammation is required to induce similar immune changes to those observed in PTSD patients in this model.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs Hospital, La Jolla, CA, USA.
Jessica
J
Deslauriers
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Netherlands.
Myrthe
M
van Wijngaarde
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs Hospital, La Jolla, CA, USA.
Mark A
MA
Geyer
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs Hospital, La Jolla, CA, USA. Electronic address: spowell@ucsd.edu.
Susan
S
Powell
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs Hospital, La Jolla, CA, USA. Electronic address: vrisbrough@ucsd.edu.
Victoria B
VB
Risbrough
D000818:Animals; D001007:Anxiety / Q000276:immunology; D001362:Avoidance Learning; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013313:Stress Disorders, Post-Traumatic / Q000276:immunology* / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D002097:C-Reactive Protein
Avoidance behaviors; Inflammation; Lipopolysaccharide; PTSD; Predator stress