苯妥英(phenytoin)是一種全世界廣泛使用的抗癲癇藥物,，最近在躁郁癥病人的臨床研究顯示，和其他治療躁郁癥病人的抗痙攣藥物如carbamazepine或valproate比較,，苯妥英除了有抗痙攣的效果外,，可能還多一個穩(wěn)定情緒的作用。在2010年三月份實驗生物及醫(yī)學(xué)(Experimental Biology and Medicine)期刊發(fā)表的研究，Veronica Mariotti 及同事利用DNA微陣列技術(shù)在大鼠腦部找尋受苯妥英作用而影響的基因表達,，探討可能影響情緒穩(wěn)定的分子基礎(chǔ),。
和未處理的動物比較，苯妥英治療一個月的大鼠在下視丘多了508個不同的基因表達,，在額葉皮質(zhì)區(qū)多了62個基因,，這些基因參與包括GABA受體、麩氨酸神經(jīng)傳導(dǎo),、神經(jīng)保護,、以及其他被認(rèn)為和調(diào)節(jié)情緒有關(guān)的基因，有些基因和傳統(tǒng)穩(wěn)定情緒的藥物如鋰鹽或Valproate 所調(diào)節(jié)的基因是一樣的,。
因此這研究的發(fā)現(xiàn)指出長期服用苯妥英可以改變參與情緒調(diào)節(jié)的基因,，以及已知可以穩(wěn)定情緒的基因表達，Mariotti博士說明"這研究提供一個初步的結(jié)果了解苯妥英有潛力作為一個情緒穩(wěn)定劑的分子作用機制,，或是更廣泛地,，雙極性躁郁癥的病態(tài)生理。"
這研究是意大利比薩大學(xué)醫(yī)學(xué)院實驗病理系分子生物學(xué)實驗室的Silvia Pellegrini博士和以色列貝爾謝巴的內(nèi)蓋夫本－古里安大學(xué)健康科學(xué)院精神科部門的Galila Agam以及R.H. Belmaker教授的實驗室共同合作的成果,。
實驗生物及醫(yī)學(xué)期刊主編Steven R. Goodman說,"Mariotti及同事提供大鼠給予苯妥英后在基因表達上非常有趣的結(jié)果,，這發(fā)現(xiàn)有助于我們了解使用這個抗癲癇藥物帶來改變情緒的效果。"(生物谷Bioon.com)
生物谷推薦原文：
Exp.Biol.Med. 2010;235:300-310 doi:10.1258/ebm.2009.009225
Effect of prolonged phenytoin administration on rat brain gene expression assessed by DNA microarrays
Veronica Mariotti1, Erika Melissari1, Shirly Amar2, Angela Conte3, Robert Haim Belmaker2, Galila Agam2, and Silvia Pellegrini1,
Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also be beneficial for treatment of bipolar disorder. To examine molecular mechanisms of action of phenytoin as a potential mood stabilizer, DNA microarrays were used to study the effect of phenytoin on gene expression in the hippocampus and frontal cortex of Sprague–Dawley rats. While our particular interest is in bipolar disorder, this is the first DNA microarray study on the effect of phenytoin in brain tissue, in general. As compared with control rats, treated rats had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex. Phenytoin modulated the expression of genes which may affect neurotransmission, e.g. glutamate decarboxylase 1 (Gad1) and -aminobutyric acid A receptor, alpha 5 (Gabra5). Phenytoin also exerted an effect on neuroprotection-related genes, namely the survival-promoting and antioxidant genes v-akt murine thymoma viral oncogene homolog 1 (Akt1), FK506 binding protein 12-rapamycin associated protein 1 (Frap1), glutathione reductase (Gsr) and glutamate cysteine ligase catalytic subunit (Gclc). The expression of genes potentially associated with mechanisms of mood regulation such as adenylate cyclase-associated protein 1 (Cap1), Glial Fibrillary Acidic Protein (Gfap) and prodynorphin (Pdyn) was also altered. Some of the above genes are regarded as targets of classical mood stabilizers and their modulation supports the clinical observation that phenytoin may have mood-stabilizing effects. The results may provide new insights regarding the mechanism of action of phenytoin and genes found differentially expressed following phenytoin administration may play a role in the pathophysiology of either bipolar disorder or epilepsy.
