Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase.
Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase.
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中央昼夜节律起搏器输出的偏侧化：外周振荡器相位的神经控制测试。
DOI：
10.1152/ajpregu.00746.2009
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Bittman,EricL
中科院分区：
文献类型：
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作者：
Mahoney,CarrieE;Brewer,Daniel;Costello,MaryK;Brewer,JudyMcKinley;Bittman,EricL
为了评估神经通路对确定外周器官昼夜节律振荡相位的贡献，我们评估了叙利亚仓鼠中通过暴露于恒定光而诱导的运动活动节律分裂的时钟基因表达的偏侧化。我们在预测活动开始 (pAO) 之前每隔 3 小时测量高侧与低侧 (H/L) 的 haPer1、haPer2 和 haBmal1 mRNA 比率。我们还计算了表达higherhaPer1的视交叉上核(SCN)一侧的同侧与对侧(I/C)的表达。分裂仓鼠的不对称程度因特定基因、阶段和器官而异。尽管周围器官的不对称程度从来没有SCN那么大，但我们观察到，与未分割的对照相比，分割仓鼠的肾上腺髓质和皮质、肺和骨骼肌中时钟基因表达的偏侧化明显更大，但肝脏或肾脏中则不然。我们观察到骨骼肌中时钟控制基因、白蛋白位点 D 元件结合蛋白 (Dbp) 的表达有五倍偏侧化（H/L：3 小时时为 10.7 ± 3.7，pAO 0 时为 2.2 ± 0.3；P= 0.03）。此外，分裂仓鼠的肾上腺髓质（H/L：0小时时1.9±0.5）与未分裂仓鼠（1.2±0.04；P<0.05）的肾上腺髓质中酪氨酸羟化酶表达不对称。与神经控制基因表达模型一致，我们发现早晨和晚上成分之间的相位角 (ψme) 与不对称水平（H/L 或 I/C）之间存在显着相关性。我们的结果表明，神经通路有助于但不能完全解释 SCN 对周围振荡器相位的调节。
To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio ofhaPer1,haPer2, andhaBmal1mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higherhaPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein (Dbp), in skeletal muscle (H/L: 10.7 ± 3.7 at 3 h vs. 2.2 ± 0.3 at 0 h pAO;P= 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 ± 0.5 at 0 h) vs. unsplit hamsters (1.2 ± 0.04;P< 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (ψme) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.