Dopamine receptor-mediated regulation of neuronal "clock" gene expression.
Dopamine receptor-mediated regulation of neuronal "clock" gene expression.
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DOI：
10.1016/j.neuroscience.2008.10.044
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发表时间：
2009-01-23
期刊：
影响因子：
3.3
通讯作者：
Uz, T.
中科院分区：
文献类型：
--
作者：
Imbesi, M.;Yildiz, S.;Arslan, A. Dirim;Sharma, R.;Manev, H.;Uz, T.
使用转基因小鼠模型（即，“时钟”敲除），时钟转录因子被认为是药物滥用诱导的多巴胺能行为的关键调节因子。此外，已经表明，全身施用精神兴奋剂，如可卡因和甲基苯丙胺，调节纹状体生物钟基因的表达。然而，多巴胺受体是否在细胞水平上介导精神兴奋剂的这些调节作用尚不清楚。原代培养的纹状体神经元表达多巴胺受体和时钟基因，并已成功地用于研究多巴胺受体功能。因此，我们研究了多巴胺受体对神经元时钟基因表达的作用，在这个模型中使用特定的受体激动剂。我们发现D2类（即，D2/D3）受体激动剂喹吡罗。我们还发现了对时钟基因mPer 1、mClock、mNPAS 2和mBmal 1表达的一般性刺激作用，其中D1类（即，D1）受体激动剂SKF 38393。此外，我们测试了多巴胺受体激动剂的全身给药是否会引起体内纹状体时钟基因表达的类似变化。我们发现喹吡罗诱导的小鼠纹状体中mPER 1蛋白水平的改变（即，节律移位）。总的来说，我们的研究结果表明，DA受体系统可能介导的精神兴奋剂诱导的时钟基因表达的变化。使用培养物中的纹状体神经元作为模型，需要进一步的研究来更好地理解多巴胺信号传导如何调节时钟基因的表达动态（即，细胞内信号传导途径），从而影响神经元基因表达、神经元传递和脑功能。
Using transgenic mice model (i.e., “clock” knockouts), clock transcription factors have been suggested as critical regulators of dopaminergic behaviors induced by drugs of abuse. Moreover, it has been shown that systemic administration of psychostimulants, such as cocaine and methamphetamine regulate the striatal expression of clock genes. However, it is not known whether dopamine receptors mediate these regulatory effects of psychostimulants at the cellular level. Primary striatal neurons in culture express dopamine receptors as well as clock genes and have been successfully used in studying dopamine receptor functioning. Therefore, we investigated the role of dopamine receptors on neuronal clock gene expression in this model using specific receptor agonists. We found an inhibitory effect on the expression of mClock and mPer1 genes with the D2-class (i.e., D2/D3) receptor agonist quinpirole. We also found a generalized stimulatory effect on the expression of clock genes mPer1, mClock, mNPAS2, and mBmal1 with the D1-class (i.e., D1) receptor agonist SKF38393. Further, we tested whether systemic administration of dopamine receptor agonists causes similar changes in striatal clock gene expression in vivo. We found quinpirole-induced alterations in mPER1 protein levels in the mouse striatum (i.e., rhythm shift). Collectively, our results indicate that the DA receptor system may mediate psychostimulant-induced changes in clock gene expression. Using striatal neurons in culture as a model, further research is needed to better understand how dopamine signaling modulates the expression dynamics of clock genes (i.e., intracellular signaling pathways) and thereby influences neuronal gene expression, neuronal transmission, and brain functioning.
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影响因子：
7.6
作者：
Uz, T;Akhisaroglu, M;Manev, H
通讯作者：
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