RESUMEN
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.
Asunto(s)
Ansiedad/etiología , Ansiedad/patología , Hipocampo/citología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Dominios PDZ/fisiología , Estrés Psicológico/complicaciones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Animales Recién Nacidos , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Corticosterona/metabolismo , Corticosterona/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Proteínas Asociadas a Microtúbulos/metabolismo , Pirrolidinas/farmacología , Transducción de Señal/fisiología , Estrés Psicológico/patología , Tiocarbamatos/farmacología , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Proteínas ras/metabolismoRESUMEN
Based on the microorganism kinetic model, the formula for computing hydraulic retention time in a membrane bioreactor system (MBR) is derived. With considering HRT as an evaluation index a combinational approach was used to discuss factors which have an effect on MBR. As a result, the influencing factors were listed in order from strength to weakness as: maximum specific removal rate K, saturation constant Ks, maintenance coefficient m, maximum specific growth rate mu m and observed yield coefficient Yobs. Moreover, the formula was simplified, whose parameters were experimentally determined in petrochemical wastewater treatment. The simplified formula is theta = 1.1(1/beta-1) (Ks + S)/KX0, for petrochemical wastewater treatment K and Ks equaled 0.185 and 154.2, respectively.