Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity
Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity
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DOI：
10.1210/en.2007-0526
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Raison, Sylvie
中科院分区：
文献类型：
--
作者：
Malek, Zeina S.;Sage, Dominique;Raison, Sylvie
色氨酸羟化酶（TPH，血清素合成的限速酶）蛋白和 mRNA 水平在大鼠背侧和中缝中呈现昼夜节律表达。这些模式表明血清素在视交叉上核主时钟的控制下有节奏地合成。在本研究中，我们通过定量原位杂交检查了主时钟的内分泌和行为输出信号对 Tph2 mRNA 水平的影响。在没有肾上腺的情况下，在中缝背侧和中缝中观察到 Tph2 mRNA 节律在 24 小时内完全受到抑制。肾上腺切除大鼠中皮质酮每日变化的恢复从头诱导了 Tph2 mRNA 节律模式，表明 Tph2 mRNA 节律依赖于糖皮质激素的每日波动。 6 周期间自主运动活动的增强增加了对照大鼠两个中缝核中 Tph2 mRNA 的水平，但血浆皮质酮水平并未同时增加。此外，这种长期增强的运动活性能够恢复肾上腺切除大鼠中 Tph2 mRNA 的显着变化。总之，内分泌和行为线索都可以调节中缝背侧和中缝中 Tph2 的表达。皮质酮激增充当节律性提示，诱导中缝神经元中 Tph2 的节律性表达。另一方面，长期运动会调节该基因的表达水平。因此，血清素神经元是内分泌和行为昼夜节律线索的目标，并且视交叉上核的血清素能输入可能反馈并影响生物钟本身的功能。
Tryptophan hydroxylase (TPH, the rate-limiting enzyme of serotonin synthesis) protein and mRNA levels display a circadian expression in the rat dorsal and median raphe. These patterns suggest a rhythmic synthesis of serotonin under the control of the master clock of suprachiasmatic nuclei. In the present study, we examined the involvement of endocrine and behavioral output signals of the master clock upon the Tph2 mRNA levels by quantitative in situ hybridization. In the absence of adrenals, a complete suppression of Tph2 mRNA rhythm was observed in dorsal and median raphe over 24 h. The restoration of corticosterone daily variations in adrenalectomized rats induced a Tph2 mRNA rhythmic pattern de novo, indicating that Tph2 mRNA rhythm is dependent upon daily fluctuations of glucocorticoids. Enhanced voluntary locomotor activity during 6 wk increased the level of Tph2 mRNA in both raphe nuclei of control rats without concomitant increase of corticosterone plasma levels. Moreover, this long-term enhanced locomotor activity was able to restore significant variation of Tph2 mRNA in adrenalectomized rats. In conclusion, both endocrine and behavioral cues can modulate Tph2 expression in dorsal and median raphe. The corticosterone surge acts as a rhythmic cue that induces the rhythmic expression of Tph2 in the raphe neurons. On the other hand, long-term exercise modulates the expression levels of this gene. Thus, the serotonin neurons are a target for both endocrine and behavioral circadian cues, and the serotoninergic input to the suprachiasmatic nuclei might feedback and influence the functioning of the clock itself.