Glucocorticoid status affects antidepressant regulation of locus coeruleus tyrosine hydroxylase and dorsal raphé tryptophan hydroxylase gene expression.
Glucocorticoid status affects antidepressant regulation of locus coeruleus tyrosine hydroxylase and dorsal raphé tryptophan hydroxylase gene expression.
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糖皮质激素状态会影响抗抑郁药的抗抑郁药调节果岭酪氨酸羟化酶和背raphé色氨酸羟化酶基因表达。
DOI：
10.1016/j.brainres.2009.06.082
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发表时间：
2009-09-08
期刊：
影响因子：
2.9
通讯作者：
Jacobson L
中科院分区：
文献类型：
--
作者：
Heydendael W;Jacobson L
脑干单胺能核表达糖皮质激素受体（GR），糖皮质激素已被证明可以抑制参与单胺合成的酶的表达。单胺缺乏与抑郁症病理有关。然而，尚不清楚抗抑郁药是否调节脑干 GR，以及糖皮质激素是否可能影响单胺合成酶的抗抑郁作用。我们的实验室发现单胺氧化酶抑制剂苯乙肼和三环类抗抑郁药丙咪嗪对 HPA 活性和前脑 GR 表达具有相反的作用。因此，我们假设苯乙肼和丙咪嗪也会对脑干 GR 基因表达产生差异性影响，并且抗抑郁药诱导的 GR 表达变化可能与对单胺合成酶表达的影响相关。使用原位杂交，我们测量了长期抗抑郁治疗对雄性 C57BL/6 小鼠脑干 GR、蓝斑和腹侧被盖区 (VTA) 酪氨酸羟化酶 (TH) 和中缝背侧色氨酸羟化酶 (TPH2) 基因表达的影响，这些小鼠的肾上腺被切除并用规定水平的皮质酮替代。苯乙肼可降低蓝斑中的 GR 表达，并可降低中缝背侧的丙咪嗪的 GR 表达。苯乙肼以糖皮质激素依赖性方式增加蓝斑 TH 和丙咪嗪增加中缝背侧 TPH2 基因表达，表明这些酶的增加是由于抑制性糖皮质激素信号传导的缓解。我们没有发现对 VTA 中 GR 或 TH 表达或任何检查的细胞核中 MR 表达有抗抑郁作用。我们的研究结果代表了一种潜在机制，抗抑郁药和糖皮质激素可以通过影响脑干 GR、去甲肾上腺素和血清素来改变 HPA 活性和情绪。
Brainstem monoaminergic nuclei express glucocorticoid receptors (GR), and glucocorticoids have been shown to inhibit expression of enzymes involved in monoamine synthesis. Monoamine deficits have been implicated in depression pathology. However, it is unknown if antidepressants regulate brainstem GR, and if glucocorticoids might influence antidepressant effects on monoamine-synthesizing enzymes. Our lab has found opposing effects of the monoamine oxidase inhibitor phenelzine and the tricyclic antidepressant imipramine on HPA activity and forebrain GR expression. We therefore hypothesized that phenelzine and imipramine would also affect brainstem GR gene expression differentially, and that antidepressant-induced changes in GR expression would correlate with effects on monoamine-synthesizing enzyme expression. Using in situ hybridization, we measured effects of chronic antidepressant treatment on brainstem GR, locus coeruleus and ventral tegmental area (VTA) tyrosine hydroxylase (TH), and dorsal raphé tryptophan hydroxylase (TPH2) gene expression in male C57BL/6 mice that were adrenalectomized and replaced with defined levels of corticosterone. GR expression was decreased by phenelzine in the locus coeruleus and decreased by imipramine in the dorsal raphé. Phenelzine increased locus coeruleus TH and imipramine increased dorsal raphé TPH2 gene expression in a glucocorticoid-dependent manner, suggesting that increases in these enzymes were due to relief of inhibitory glucocorticoid signaling. We did not find antidepressant effects on GR or TH expression in the VTA or on MR expression in any of the nuclei examined. Our findings represent a potential mechanism through which antidepressants and glucocorticoids could alter both HPA activity and mood via effects on brainstem GR, norepinephrine, and serotonin.
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影响因子：
2.9
作者：
Castonguay, TW;Beaulieu, S;Brown, L
通讯作者：
Brown, L
影响因子：
15.9
作者：
BRADY, LS;WHITFIELD, HJ;HERKENHAM, M
通讯作者：
HERKENHAM, M
DOI：
10.1016/s0169-328x(97)00106-x
发表时间：
1997-09-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Clark, MS;Russo, AF
通讯作者：
Russo, AF
影响因子：
11
作者：
Anisman, H;Ravindran, AV;Merali, Z
通讯作者：
Merali, Z
影响因子：
5.6
作者：
Drevets, WC;Bogers, W;Raichle, ME
通讯作者：
Raichle, ME