Lu X H, Li L J, Li C Q, Luo X G
Mental Health Institute, Hunan Medical University, Changsha 410011.
Hunan Yi Ke Da Xue Xue Bao. 2000 Dec 28;25(6):535-8.
This study was to explore the therapeutic potential of c-fos antisense phosphorothioate oligonucleotide and the possible molecular mechanism.
On the basis of the sequence of c-fos mRNA, two 15-mer phosphorothioated oligodeoxynucleotide(ODN) were synthesized. Antisense ODN was corresponded to the initiation codon of c-fos mRNA. The complementary sense and vehicle(saline) served as controls. Anxiety was induced in rats by a social-defeated paradigm and then rats were given a 5-minute exposure to the plus maze and open field test. Rats were injected c-fos antisense, sense ODNs and vehicles into the lateral ventricle through stainless-steel guide cannulate implanted unilaterally from the beginning of the experiment. The expression of the protein product of the immediate early gene c-fos was analyzed with immunochemistry in different brain regions, such as the amygdala and paraventricularis hypothalami nucleus. Computer assisted image analysis was performed to quantify the results of immuno-cytochemistry.
Socially defeated c-fos antisense-treated rats displayed obviously reduced anxiety-related behavior, as they spent significantly more time in the open arms of the plus maze compared to sense ODN- and vehicle-treated rats. The behavioral effects were similar to those of established anti-anxiety drugs(diazepam). Antisense oligodeoxynucleotide significantly decreased Fos positive nucleus in paraventricularis hypothalami nucleus. The inhibitory efficiency was 57.03%.
Our data provide further evidence that c-fos is involved in acute stress elicited anxiety related behavior.
本研究旨在探索c-fos反义硫代磷酸酯寡核苷酸的治疗潜力及其可能的分子机制。
根据c-fos mRNA的序列，合成了两条15聚体硫代磷酸化寡脱氧核苷酸（ODN）。反义ODN对应于c-fos mRNA的起始密码子。互补正义链和溶剂（生理盐水）作为对照。通过社会挫败范式诱导大鼠产生焦虑，然后让大鼠在加迷宫和旷场试验中暴露5分钟。从实验开始，通过单侧植入的不锈钢导套管将c-fos反义、正义ODN和溶剂注入大鼠侧脑室。采用免疫化学方法分析杏仁核和下丘脑室旁核等不同脑区即刻早期基因c-fos蛋白产物的表达。进行计算机辅助图像分析以量化免疫细胞化学结果。
社会挫败的c-fos反义处理大鼠表现出明显减少的焦虑相关行为，与正义ODN和溶剂处理的大鼠相比，它们在加迷宫开放臂中花费的时间明显更多。行为学效应与已有的抗焦虑药物（地西泮）相似。反义寡脱氧核苷酸显著降低了下丘脑室旁核中Fos阳性核的数量。抑制效率为57.03%。
我们的数据进一步证明c-fos参与了急性应激引发的焦虑相关行为。
