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• W3209746617 endingPage "113647" @default.
• W3209746617 startingPage "113647" @default.
• W3209746617 abstract "Chronic stress is one of the most important causes of depression, accompanied by neuroinflammation and hippocampal injuries. Long-term elevation of glucocorticoid leads to activation of NF-κB and inhibition of GPR39/CREB/BDNF pathway, which is pivotal for neuroprotection and neurogenesis. The present study thus was designed to determine the relationship between NF-κB and GPR39/CREB/BDNF pathway.Depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) in mice. Corticosterone, inflammatory cytokines, and GPR39/CREB/BDNF pathway were determined by ELISA and Western Blot assays. The activation of NF-κB and inhibition of GPR39 were connected by bioinformatic analysis and experimentally validated in hippocampus cells by knock-in and knock-down techniques.CUMS and CRS led to an elevation of serum corticosterone and depressive-like behaviors in mice, with activation of NF-κB subunit p65 in the hippocampus and elevations of TNFα and IL-6. The expression of GPR39/CREB/BDNF pathway in the hippocampus was inhibited. Bioinformatic analysis revealed that four miRNAs, miR-96, miR-143, miR-150, and miR-182, were potentially transcribed by NF-κB and bound with GPR39 mRNA. NF-κB overexpression increased miR-182 expression and decreased GPR39 expression in hippocampus cells. Its inhibitor led to reverse effects. miR-182 mimics or inhibitors also regulated GPR39 expression in hippocampus cells and more importantly, blocked the regulation of NF-κB on GPR39.The results suggested that activation of NF-κB inhibited GPR39/CREB/BDNF pathway through increasing miR-182 in chronic stress-induced depressive-like behaviors. The negative-regulation features of miRNAs might be important for neuroinflammation-induced inhibition of neurofunction in depression." @default.
• W3209746617 created "2021-11-08" @default.
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• W3209746617 date "2022-02-01" @default.
• W3209746617 modified "2023-10-18" @default.
• W3209746617 title "miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors" @default.
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• W3209746617 doi "https://doi.org/10.1016/j.bbr.2021.113647" @default.
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