Effects of c-fos antisense oligodeoxynucleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons.
Effects of c-fos antisense oligodeoxynucleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons.
复制标题
DOI：
10.1016/j.bbrc.2003.08.046
复制
发表时间：
2003-09
影响因子：
3.1
通讯作者：
Y. Wang;S. Wu;X-Y Liu;W. Wang;Y. Li
中科院分区：
文献类型：
--
作者：
Y. Wang;S. Wu;X-Y Liu;W. Wang;Y. Li
c-fos反义寡核苷酸（阿索）对5-羟色胺（5-HT）诱导的前强啡肽原（ppDyn）、前脑啡肽原（ppEnk）和γ-氨基丁酸（GABA）神经元特异性化学标记物谷氨酸脱羧酶（GAD）上调的影响本研究通过对体外培养的脊髓背角神经元中阿片肽和γ-氨基丁酸（GABA）mRNA的研究，进一步了解阿片肽和GABA在脊髓背角神经元中的表达，肾上腺素能传出神经。逆转录-聚合酶链反应分析显示，5-HT（100 nM）给药后，编码c-fos，ppDyn，ppEnk和GAD的mRNA表达随时间推移而增加。5-HT预处理前30 min给予c-fos阿索寡核苷酸（0.02nM）可明显抑制c-fos基因的表达。c-fos阿索寡核苷酸预处理可显著降低5-HT诱导的ppDyn和ppEnk mRNA表达上调，但对GAD mRNA表达水平无影响。这些结果提示，中缝核-脊髓传出神经可能在调节脊髓背角神经元脑啡肽、强啡肽和GABA的合成中起重要作用。即早癌基因c-fos可能参与了5-HT诱导的ppDyn和ppEnk表达的增加。然而，在本实验条件下，c-fos似乎并不与5-HT诱导的GAD mRNA的上调。
Effects of c-fos antisense oligodeoxynucleotide (ASO) on serotonin (5-HT)-induced upregulation of preprodynorphin (ppDyn), preproenkephalin (ppEnk), and glutamic acid decarboxylase (GAD), a special chemical marker for γ-aminobutyric acid (GABA) neurons, mRNAs in cultured spinal dorsal horn neurons were investigated in order to extend our understanding of expressions of opioid peptides and GABA in spinal cord regulated by the descending serotonergic efferents. Reverse transcription-polymerase chain reaction analysis revealed a time-course increase in the expression of mRNAs encoding c-fos, ppDyn, ppEnk, and GAD after administration of 5-HT (100nM). Administration of c-fos ASO (0.02nM) 30min prior to 5-HT application markedly blocked the expression of c-fos gene. Moreover, c-fos ASO pretreatment significantly decreased the 5-HT-induced upregulation of ppDyn and ppEnk mRNAs, but failed to affect the expression level of GAD mRNA. These results suggest that the serotoningic raphe-spinal efferents might play an important role in regulating the synthesis of enkephalin, dynorphin, and GABA in the spinal dorsal horn neurons. The immediate early oncogene c-fos might be involved in the 5-HT-induced increase in ppDyn and ppEnk expression. However, under the present experimental conditions, c-fos does not seem to be associated with the upregulation of GAD mRNA induced by 5-HT.