小鼠Per2基因的昼夜节律表达与神经干细胞增殖之间的相关性关联。
Correlative association between circadian expression of mousePer2 gene and the proliferation of the neural stem cells.
作者信息
Moriya T, Hiraishi K, Horie N, Mitome M, Shinohara K
机构信息
Department of Neurobiology and Behavior, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-3-5 Sakamoto, Nagasaki, Japan.
出版信息
Neuroscience. 2007 May 11;146(2):494-8. doi: 10.1016/j.neuroscience.2007.02.018. Epub 2007 Mar 26.
We examined the circadian expression of mousePeriod (mPer) genes (mPer1 and mPer2) and the proliferation of the neural stem cells in vitro. The neural stem cells from the ganglionic eminence of embryonic mice were expanded by the neurosphere method and then treated with epidermal growth factor (EGF) to stimulate their mitotic activity. The time courses of the proliferation were examined by WST-8 assay and bromodeoxyuridine (BrdU) incorporation assay and the expression of mPer1 and mPer2 genes was examined by RT-PCR and immunocytochemistry. We have found that EGF treatment elicited the circadian change in both the increase in viable cell number and DNA synthesis activity of the neural stem cells. Also, the gene expression of mPer2, but not mPer1, changed rhythmically with a period of 24 h and correlated negatively with the DNA synthesis activity rhythm. Furthermore, the treatment with an antisense oligonucleotide against mPer2 increased the DNA synthesis activity of the neural stem cells. These results suggest that mPer2 might periodically suppress the proliferation of neural stem cells.
我们检测了小鼠周期基因（mPer）（mPer1和mPer2）的昼夜节律表达以及神经干细胞在体外的增殖情况。通过神经球法扩增来自胚胎小鼠神经节隆起的神经干细胞，然后用表皮生长因子（EGF）处理以刺激其有丝分裂活性。通过WST-8检测和溴脱氧尿苷（BrdU）掺入检测来检测增殖的时间进程，通过RT-PCR和免疫细胞化学来检测mPer1和mPer2基因的表达。我们发现，EGF处理引发了神经干细胞活细胞数量增加和DNA合成活性的昼夜变化。此外，mPer2而非mPer1的基因表达以24小时为周期有节律地变化，并且与DNA合成活性节律呈负相关。此外，用针对mPer2的反义寡核苷酸处理增加了神经干细胞的DNA合成活性。这些结果表明，mPer2可能周期性地抑制神经干细胞的增殖。
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