Altered Expression of Phox2 Transcription Factors in the Locus Coeruleus in Major Depressive Disorder Mimicked by Chronic Stress and Corticosterone Treatment In Vivo and In Vitro.
Altered Expression of Phox2 Transcription Factors in the Locus Coeruleus in Major Depressive Disorder Mimicked by Chronic Stress and Corticosterone Treatment In Vivo and In Vitro.
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DOI：
10.1016/j.neuroscience.2018.09.038
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发表时间：
2018-11-21
期刊：
影响因子：
3.3
通讯作者：
Zhu MY
中科院分区：
文献类型：
--
作者：
Fan Y;Chen P;Raza MU;Szebeni A;Szebeni K;Ordway GA;Stockmeier CA;Zhu MY
Phox2a 和 Phox2b 是两种同源域转录因子，在胚胎期去甲肾上腺素能神经元的发育中发挥着关键作用。然而，它们在成年后的表达和功能仍有待阐明。本研究使用人类死后脑组织、大鼠应激模型和培养细胞，旨在检查 Phox2a 和 Phox2b 表达的变化。结果表明，Phox2a和Phox2b在成年期的人类蓝斑（LC）中正常表达。此外，与年龄匹配且精神正常的对照供体相比，患有重度抑郁症的脑供体的 LC 中 Phox2a 蛋白水平以及 Phox2b mRNA 和蛋白水平显着升高。与未受到压力的对照大鼠相比，遭受慢性社交失败的 Fischer 344 只大鼠在 LC 中表现出更高的 Phox2a 和 Phox2b mRNA 和蛋白质水平。在长期口服皮质酮的大鼠中，LC 中 Phox2b（而非 Phox2a）的 mRNA 和蛋白质水平显着增加。此外，同时使用米非司酮或螺内酯治疗可逆转皮质酮诱导的 Phox2b 蛋白增加。将 SH-SY5Y 细胞暴露于皮质酮可显着增加 Phox2a 和 Phox2b 的表达，而皮质类固醇受体拮抗剂可阻断这种表达。总而言之，这些实验表明，Phox2 基因在人类和 Fischer 344 大鼠的 LC 中终生表达。它们表达的改变可能通过其对去甲肾上腺素能表型的调节作用在重度抑郁症和可能的其他压力相关疾病中发挥作用。
Phox2a and Phox2b are two homeodomain transcription factors playing a pivotal role in the development of noradrenergic neurons during the embryonic period. However, their expression and function in adulthood remain to be elucidated. Using human postmortem brain tissues, rat stress models and cultured cells, this study aimed to examine the alteration of Phox2a and Phox2b expression. The results show that Phox2a and Phox2b are normally expressed in the human locus coeruleus (LC) in adulthood. Furthermore, the levels of Phox2a protein and mRNA and protein levels of Phox2b were significantly elevated in the LC of brain donors that suffered from the major depressive disorder, as compared to age-matched and psychiatrically normal control donors. Fischer 344 rats subjected to chronic social defeat showed higher mRNA and protein levels of Phox2a and Phox2b in the LC, as compared to non-stressed control rats. In rats chronically administered oral corticosterone, mRNA and protein levels of Phox2b, but not Phox2a, in the LC were significantly increased. In addition, the corticosterone-induced increase of Phox2b protein was reversed by simultaneous treatment with either mifepristone or spironolactone. Exposing SH-SY5Y cells to corticosterone significantly increased expression of Phox2a and Phox2b, which was blocked by corticosteroid receptor antagonists. Taken together, these experiments reveal that Phox2 genes are expressed throughout the lifetime in the LC of humans and Fischer 344 rats. Alterations in their expression may play a role in major depressive disorder and possibly other stress-related disorders through their modulatory effects on the noradrenergic phenotype.
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影响因子：
3.4
作者：
Golde, S;Coles, A;Compston, A
通讯作者：
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影响因子：
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作者：
Fan Y;Chen P;Li Y;Cui K;Noel DM;Cummins ED;Peterson DJ;Brown RW;Zhu MY
通讯作者：
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影响因子：
10.6
作者：
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影响因子：
16.2
作者：
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通讯作者：
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DOI：
10.1007/s00406-008-0825-8
发表时间：
2008-12-01
影响因子：
4.7
作者：
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通讯作者：
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