IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression

Hyper-inflammatory reaction plays a crucial role in the pathophysiology of depression and anxiety disorders. However, the mechanisms underlying inflammation-induced anxiety changes remain poorly understood. Here, we showed that in the lipopolysaccharide (LPS)-induced anxiety model, Interleukin (IL)-33, a member of the IL-1 family, was up-regulated in the basolateral amygdala, and IL-33 deficiency prevent anxiety-like behavior. Overexpression of IL-33 in amygdalar astrocytes led to anxiety-like response via repressing brain-derived neurotrophic factor (BDNF) expression. Mechanically, IL-33 suppressed BDNF expression through NF-kappa B pathway to impair GABAergic transmission in the amygdala and NF-kappa B inhibitor abolished the effect of IL-33 on anxiety. Administration of an inverse GABAA receptor agonist increased the anxiety of IL-33-deficient mice. These results reveal that inflammatory response can activate anxiogenic circuits by suppressing BDNF and GABAergic neurons transmission, suggesting that IL-33 in basolateral amygdalar is a linker between inflammation and anxiety.

Automated summary

Hyper-inflammatory reaction can activate anxiety circuits by suppressing BDNF and GABAergic neurons transmission.