Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin.
Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin.
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DOI：
10.1111/j.1528-1167.2010.02545.x
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发表时间：
2010-09
期刊：
影响因子：
5.6
通讯作者：
Dingledine R
中科院分区：
文献类型：
--
作者：
Hassel B;Taubøll E;Shaw R;Gjerstad L;Dingledine R
一般认为，只要抗癫痫药物的分子靶点存在，抗癫痫药物（aed）在大脑各部分的作用是相似的。一些关于维加巴特林、左乙拉西坦、丙戊酸和拉莫三嗪代谢作用的实验研究表明，这些药物在不同的大脑区域可能有不同的作用。我们研究了左乙拉西坦或苯妥英慢性治疗对mRNA水平的影响，以广泛、无偏倚的方式检测局部药物效应。用基于寡核苷酸的微阵列监测三个脑区的mRNA水平。左乙拉西坦（150 mg/kg，连续90 d）改变了脑桥/延髓中65个基因的表达，海马中2个基因，额叶皮层中1个基因的表达。而苯妥英（75 mg/kg）只改变了脑桥/延髓中3个基因的表达，海马中64个基因的表达，额叶皮层中327个基因的表达。在对基因表达的影响方面，观察到区域或药物治疗之间很少重叠。我们的结论是，长期使用左乙拉西坦或苯妥英治疗会对大脑中的基因表达产生区域特异性和高度差异的影响。基因表达的区域效应反映了aed分子靶点的区域差异，并可能影响aed的临床特征。
It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner. mRNA levels were monitored in three brain regions with oligonucleotide-based microarrays. Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression. We conclude that chronic treatment with levetiracetam or phenytoin causes region-specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs.
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影响因子：
5.6
作者：
Lukyanetz, EA;Shkryl, VM;Kostyuk, PG
通讯作者：
Kostyuk, PG
影响因子：
2.9
作者：
Loscher, W;Honack, D;BlomsFunke, P
通讯作者：
BlomsFunke, P
影响因子：
2.9
作者：
NOEBELS, JL;RUTECKI, PA
通讯作者：
RUTECKI, PA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
11.2
作者：
Bough, Kristopher J.;Wetherington, Jonathon;Dingledine, Raymond J.
通讯作者：
Dingledine, Raymond J.