1. IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression.
- Author
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Zhuang X, Zhan B, Jia Y, Li C, Wu N, Zhao M, Chen N, Guo Y, Du Y, Zhang Y, Cao B, Li Y, Zhu F, Guo C, Wang Q, Li Y, and Zhang L
- Subjects
- Animals, Anxiety metabolism, Inflammation metabolism, Inflammation pathology, Mice, Neuroinflammatory Diseases metabolism, Basolateral Nuclear Complex metabolism, Basolateral Nuclear Complex pathology, Brain-Derived Neurotrophic Factor biosynthesis, Brain-Derived Neurotrophic Factor metabolism, Interleukin-33 metabolism, NF-kappa B metabolism
- Abstract
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-κB pathway to impair GABAergic transmission in the amygdala and NF-κB 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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