Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF-κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying the role of NF-κB in stress-induced anxiety behaviors are poorly understood. In this study, we show that chronic mild stress (CMS) and glucocorticoids dramatically increased the expression of NF-κB subunits p50 and p65, phosphorylation and acetylation of p65, and the level of nuclear p65 in vivo and in vitro, implicating activation of NF-κB signaling in chronic stress-induced pathological processes. Using the novelty-suppressed feeding (NSF) and elevated-plus maze (EPM) tests, we found that treatment with pyrrolidine dithiocarbamate (PDTC; intra-hippocampal infusion), an inhibitor of NF-κB, rescued the CMS- or glucocorticoid-induced anxiogenic behaviors in mice. Microinjection of PDTC into the hippocampus reversed CMS-induced up-regulation of neuronal nitric oxide synthase (nNOS), carboxy-terminal PDZ ligand of nNOS (CAPON), and dexamethasone-induced ras protein 1 (Dexras1) and dendritic spine loss of dentate gyrus (DG) granule cells. Moreover, over-expression of CAPON by infusing LV-CAPON-L-GFP into the hippocampus induced nNOS-Dexras1 interaction and anxiety-like behaviors, and inhibition of NF-κB by PDTC reduced the LV-CAPON-L-GFP-induced increases in nNOS-Dexras1 complex and anxiogenic-like effects in mice. These findings indicate that hippocampal NF-κB mediates anxiogenic behaviors, probably via regulating the association of nNOS-CAPON-Dexras1, and uncover a novel approach to the treatment of anxiety disorders.
Pubmed ID: 29858554 RIS Download
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This polyclonal targets NFkB p65
View all literature mentionsThis monoclonal targets nNOS / NOS Type I
View all literature mentionsThis unknown targets Chicken IgY(IgG) (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets IKB alpha
View all literature mentionsThis monoclonal targets Acetyl-NF-κB p65
View all literature mentionsThis polyclonal targets Phospho-NF-kappaB p65 (Ser468)
View all literature mentionsThis polyclonal targets NFkB p105 / p50 - ChIP Grade
View all literature mentionsThis polyclonal targets Rela
View all literature mentionsThis unknown targets Mouse Dexras1
View all literature mentionsThis polyclonal targets CAPON (R-300)
View all literature mentionsThis polyclonal targets Nitric Oxide Sythase I (NOS-I, bNOS, nNOS)
View all literature mentionsA Software resource for statistical analysis and presentation of graphics.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name ICR;129-Hes1tm1Fgu/KagRbrc from IMSR.
View all literature mentionsThis polyclonal targets NFkB p65
View all literature mentionsThis monoclonal targets nNOS / NOS Type I
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