التفاصيل البيبلوغرافية
| العنوان: |
miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors. |
| المؤلفون: |
Tang, Yuxiao1 (AUTHOR), Yang, Jianxin1 (AUTHOR), Ye, Chuyang1 (AUTHOR), Xu, Xin1 (AUTHOR), Cai, Mengyu1 (AUTHOR), Zhang, Yinyin1 (AUTHOR), Lu, Hongtao1 (AUTHOR), Mo, Fengfeng1 (AUTHOR), Li, Hongxia1 (AUTHOR) lihongxia@smmu.edu.cn, Shen, Hui1 (AUTHOR) shenhui@smmu.edu.cn |
| المصدر: |
Behavioural Brain Research. Feb2022, Vol. 418, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*BRAIN-derived neurotrophic factor, *MENTAL depression, *HIPPOCAMPUS (Brain), *PSYCHOLOGICAL stress, *NEUROINFLAMMATION |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
