Spexin as an anxiety regulator in mouse hippocampus: Mechanisms for transcriptional regulation of spexin gene expression by corticotropin releasing factor.
Spexin as an anxiety regulator in mouse hippocampus: Mechanisms for transcriptional regulation of spexin gene expression by corticotropin releasing factor.
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Spexin 作为小鼠海马的焦虑调节剂：促肾上腺皮质激素释放因子转录调节 Spexin 基因表达的机制。
DOI：
10.1016/j.bbrc.2020.02.023
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Zeng Guangzhi
中科院分区：
文献类型：
--
作者：
Zhuang Min;Lai Qi;Yang Chunju;Ma Yanhua;Fan Baomin;Bian Zhaoxiang;Lin Chengyuan;Bai Jin;Zeng Guangzhi
Spexin (SPX) 是一种具有多效功能的神经肽，可以参与焦虑调节。促肾上腺皮质激素释放因子（CRF）在脑组织中广泛表达，与抑郁、焦虑和成瘾有关。当焦虑小鼠处于慢性不可预知压力下时，我们发现大脑海马区SPX mRNA表达水平显着降低，而局部CRF mRNA表达水平升高。此外，在海马体内注射CRF还可以降低海马体和其他脑组织（包括垂体和下丘脑）中SPX mRNA的表达水平。在原代小鼠海马细胞模型中，CRF治疗可以降低海马细胞水平的SPX mRNA表达，并且这种抑制作用仅由促肾上腺皮质激素释放因子受体2（CRFR2）介导，而不是促肾上腺皮质激素释放因子受体1（CRFR1）介导。在 CRFR2 过表达的 HEK293 细胞中，CRF 还可以抑制与 AC/cAMP/PKA 和 MEK1/2/Erk1/2 级联偶联的 SPX 启动子活性。此外，Epac 还参与 CRF 抑制的 SPX 启动子活性并与 MEK1/2/Erk1/2 通路相互作用。 CRF可通过启动子水平的转录激活并耦合AC/cAMP和MEK1/2/Erk1/2信号通路抑制小鼠海马SPX基因的表达，这可能与SPX介导的中枢神经系统焦虑反应有关。
Spexin (SPX) acts as a neuropeptide with pleiotropic functions that can participate in anxiety regulation. Corticotropin releasing factor (CRF) is widely expressed in brain tissues and associated with depression and anxiety and addiction. With the anxious mice under chronic unpredictable stress, we found SPX mRNA expression level in the hippocampus of the brain was significantly reduced, while local CRF mRNA expression level was increased. Furthermore, CRF injection in the hippocampus could also decrease SPX mRNA expression levels in hippocampus and other brain tissues, including pituitary and hypothalamus. With the primary mouse hippocampal cell model, CRF treatment could decrease SPX mRNA expression at hippocampal cell level and this inhibitory effect was mediated only by corticotropin releasing factor receptor 2 (CRFR2) but not corticotropin releasing factor receptor 1 (CRFR1). In HEK293 cells with CRFR2 over-expression, CRF could also inhibit SPX promoter activity coupling with AC/cAMP/PKA and MEK1/2/Erk1/2cascades. In addition, Epac was also involved with the CRF-repressed SPX promoter activity and cross-talked with MEK1/2/Erk1/2pathway. CRF could inhibit SPX gene expression in mouse hippocampus via transcriptional activation at the promoter level with coupling of AC/cAMP and MEK1/2/Erk1/2signaling, which will be relevant to the anxiety response mediated by SPX in central nervous system.
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DOI：
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影响因子：
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