title: Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via enhancing inflammatory response.
abstract: Mitochondrial uncoupling protein 2 (UCP2) has been recognized as an important protein to regulate reactive oxygen species (ROS) production. The absence of UCP2 has the potential to promote ROS accumulation and thereby induces oxidative damages and inflammatory response. Increasing evidence strongly reveals that depression is accompanied by oxidative stress, so the present study was to investigate the impacts of UCP2 on the etiology of depression. Wild-type and UCP2 knockout mice were used to establish chronic mild stress (CMS)-induced anhedonia model of depression. The results showed that CMS led to more severe depressive responses in UCP2 knockout mice, characterized by exacerbated depression-like behaviors, increased corticosterone level and significant loss of weight. Moreover, CMS resulted in a higher mortality in UCP2 knockout mice. Our further study showed that UCP2 knockout enhanced CMS-induced activation of nuclear factor κB (NF-κB) p65 and increased mRNA expression of tumor necrosis factor alpha (TNF-α) in hypothalamus. And the levels of TNF-α of serum and spleen in UCP2 knockout mice are remarkably enhanced by CMS, even under basal conditions. Therefore, our findings suggest that UCP2 knockout-induced inflammation may contribute to the development of depressive symptoms.
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
authors: X-L
authors: XL
authors: Sun
authors: Y
authors: Y
authors: Liu
authors: T
authors: T
authors: Dai
authors: J-H
authors: JH
authors: Ding
authors: G
authors: G
authors: Hu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007473:Ion Channels / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2