Journal
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
Volume 23, Issue 3, Pages 308-317Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10253890.2019.1673360
Keywords
Ventral hippocampus; stress; resiliency; vulnerability; inflammation
Funding
- Defense Advanced Research Projects Agency (DARPA)
- U.S. Army Research Office [W911NF1010093]
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Mechanisms of stress vulnerability remain elusive. Previous research demonstrated that inflammation-related processes in the brain play a role in stress vulnerability. Our previous research showed that inflammatory processes in the ventral hippocampus (vHPC) induced a stress vulnerable phenotype. To further understand neuroinflammatory processes in the vHPC in stressed rats, we determined that protein levels of the pro-inflammatory cytokine interleukin-1-? (IL-1?), but not interleukin-1? (IL-1?), were increased in the vHPC of rats vulnerable to the effects of repeated social defeat compared to rats resilient to its effects. Injections of IL-1? into the vHPC increased stress vulnerability as characterized by increases in passive coping during defeat and subsequent decreased social interactions. Conversely, injections of recombinant IL-1 receptor antagonist (IL1-RA) increased latencies to social defeat and decreased anxiety-like behaviors during social interaction, suggesting an reduction in stress vulnerability. Protein analyses revealed increased FosB expression in the vHPC of IL-1?-injected rats, and increased HPA activation following a social encounter. Further analysis of vHPC of IL1-?-injected rats showed increased density of microglia, increased expression of the pro-inflammatory cytokine HMGB1, and increases in a marker for vascular remodeling. Taken together, these data show increasing IL-1? during stress exposure is sufficient to produce a stress vulnerable phenotype potentially by increasing inflammation-related processes in the vHPC.LAY SUMMARY Our previous research demonstrated that inflammation-related processes in the brain play a role in inducing vulnerability to the effects of repeated social stress in rats. Here we demonstrate that a pro-inflammatory cytokine interleukin-1-? (IL-1?) induces inflammatory processes in the vHPC and behavioral vulnerability in stressed rats, whereas blocking IL receptors produces the opposite effects on behavioral vulnerability. Together, these results identify a substrate in the vHPC that produces vulnerability to stress by increasing inflammation-related processes in the vHPC.
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