Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains.
Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains.
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DOI：
10.1016/j.neuint.2011.11.003
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发表时间：
2012-01
影响因子：
4.2
通讯作者：
Zhu, Meng-Yang
中科院分区：
文献类型：
--
作者：
Chen, Ping;Fan, Yan;Li, Ying;Sun, Zhongwen;Bissette, Garth;Zhu, Meng-Yang
关键词：
据报道，应激激活蓝斑(LC)-去甲肾上腺素系统。然而，慢性应激与去甲肾上腺素能神经元之间的分子联系仍有待阐明。在本研究中，成年Fischer 344只大鼠接受了为期4周的慢性社会失败(CSD)训练。原位杂交和Western blotting结果显示，CSD组大鼠LC区去甲肾上腺素转运体(Net)的mRNA和蛋白水平显著升高，海马区、额叶皮质和杏仁核Net蛋白水平显著升高。CSD诱导的净表达增加可被肾上腺切除或皮质类固醇受体拮抗剂治疗所消除，这表明皮质酮和皮质类固醇受体参与了这种上调。此外，通过CSD范式，LC及其末端区域的蛋白激酶A(PKA)、蛋白激酶C(PKC)和磷酸化cAMP反应元件结合(PCREB)蛋白水平显著降低。同样，CSD引起的这些蛋白质水平下降可以通过肾上腺切除来防止。然而，皮质类固醇受体拮抗剂对CSD诱导的PKA、PKC和pCREB蛋白下调的作用并不一致。虽然米非司酮和螺内酯单独或联合应用可完全阻断CSD对LC以及海马区、额叶皮质和杏仁核中PKA、PKC和pCREB蛋白水平的影响，但它们对海马区、额叶皮质和杏仁核中PKA和PKC的影响具有区域依赖性。目前的研究结果表明，慢性应激与去甲肾上腺素能系统的激活有关。这种相关性和CSD诱导的信号转导分子的改变可能解释了它们在重度抑郁症症状发展中的关键作用。
Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. In the present study adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD) for 4 weeks. Measurements by in situ hybridization and Western blotting showed that CSD significantly increased mRNA and protein levels of the norepinephrine transporter (NET) in the LC region and NET protein levels in the hippocampus, frontal cortex and amygdala. CSD-induced increases in NET expression were abolished by adrenalectomy or treatment with corticosteroid receptor antagonists, suggesting the involvement of corticosterone and corticosteroid receptors in this upregulation. Furthermore, protein levels of protein kinase A (PKA), protein kinase C (PKC), and phosphorylated cAMP-response element binding (pCREB) protein were significantly reduced in the LC and its terminal regions by the CSD paradigm. Similarly, these reduced protein levels caused by CSD were prevented by adrenalectomy. However, effects of corticosteroid receptor antagonists on CSD-induced down-regulation of PKA, PKC, and pCREB proteins were not consistent. While mifeprestone and spironolactone, either alone or in combination, totally abrogate CSD effects on these protein levels of PKA, PKC and pCREB in the LC and those in the hippocampus, frontal cortex and amygdala, their effects on PKA and PKC in the hippocampus, frontal cortex and amygdala were region-dependent. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression.
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影响因子：
--
作者：
Dwivedi, Y;Rao, JS;Pandey, GN
通讯作者：
Pandey, GN
DOI：
10.1016/j.pnpbp.2010.08.025
发表时间：
2011-06-01
影响因子：
5.6
作者：
Dwivedi, Yogesh;Pandey, Ghanshyam N.
通讯作者：
Pandey, Ghanshyam N.
影响因子：
10.6
作者：
Dwivedi, Y;Mondal, AC;Lyons, J
通讯作者：
Lyons, J
DOI：
10.1037/h0077603
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
ANISMAN, H;SKLAR, LS
通讯作者：
SKLAR, LS
影响因子：
2.9
作者：
BROSVIC, GM;RISSER, JM;DOTY, RL
通讯作者：
DOTY, RL