Talk abstracts
Talk on Tuesday 03:00-03:15pm submitted by Damon DiSabato
The neuronal IL-1b receptor is necessary and sufficient for paired fighting-induced social withdrawal and cognitive impairment
Damon DiSabato (Neuroscience Graduate Program), Daniel Nemeth (Division of Biosciences, College of Dentistry), Xiaoyu Liu (Institute for Behavioral Medicine Research), Jonathan Godbout (Department of Neuroscience, College of Medicine; Institute for Behavioral Medicine Research), Ning Quan (Division of Biosciences, College of Dentistry; Institute for Behavioral Medicine Research)
Abstract:
Stress is a well-known cause of mood disorders such as depression and anxiety. Anxiety is the most prevalent psychiatric disorder and affects upwards of a third of the population. Both microglia and peripheral myeloid cells display an inflammatory phenotype and produce increased levels of pro-inflammatory cytokines and chemokines upon exposure to chronic stress. One cytokine involved in classic inflammatory responses is interleukin-1 beta (IL-1b). IL-1b is important for a variety of biological mechanisms, and can have both adaptive and maladaptive effects. Its mRNA production is increased following exposure to psychosocial stress. Therefore, we hypothesized that IL-1b signaling in the brain is the key player in this stress-mood disorder interaction. In order to precisely dissect the role of IL-1b in such a stress model we developed a genetic tool, the IL-1R1 restore (IL-1R1r/r) mouse. This allows us to knock out IL-1R1 expression throughout the whole mouse and breed with cell type-specific Cre mice to selectively restore IL-1R1 expression. We also use IL-1 receptor floxed mice (IL-1R1f/f) to remove IL-1R1 on specific cells. Our objectives were (1) to determine the effect of PF on peripheral and central immune responses in the absence of IL-1R1, and (2) to identify if a neuron-specific IL-1R1 pathway was capable of eliciting anxiety-like behavior after PF exposure. Here, we show novel data indicating that exposure to PF was sufficient for decreased social activity, a marker of anxiety in mice, as well as microglial activation and increased trafficking of peripheral macrophages and neutrophils to the brain. These effects were not observed in IL-1R1r/r mice, indicating the requirement for IL-1R1 signaling to induce these effects. Knockout of IL-1R1 on glutamatergic cells alone was able to mimic the effects seen in global knockout mice, indicating the necessity for the neuronal IL-1 receptor in PF-induced behavioral deficits. Conversely, the presence of IL-1 receptor on glutamatergic neurons alone was sufficient to partially reproduce the behavioral deficits of PF as seen in the wild-type mice. Taken together, these data indicate that IL-1R1 expression is a critical mediator in the behavioral deficits seen after social stress, and that glutamatergic neuronal IL-1R1 is both necessary and sufficient for these effects.
Keywords: Stress, Inflammation, Anxiety