Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder
Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder
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锂反应双相情感障碍受试者培养的淋巴细胞中锂调控基因的鉴定
DOI：
10.1038/sj.npp.1300383
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发表时间：
2004
影响因子：
7.6
通讯作者：
M. Alda
中科院分区：
文献类型：
--
作者：
Xiujun Sun;L. Young;Jun;P. Grof;G. Turecki;G. Rouleau;M. Alda
锂是治疗双相情感障碍（BD）的常用药物，需要长期服用以防止疾病复发。长期治疗的必要性表明其作用机制涉及基因表达的变化。我们研究了锂对BD患者淋巴细胞基因表达的影响，这些患者均对锂预防有良好反应。使用cDNA阵列分析基因表达，共包含2400个cDNA。我们发现，在治疗相关浓度的慢性锂治疗降低了锂应答者淋巴细胞中7个基因的表达。通过Northern blotting分析，在锂反应者中验证了5个候选锂调节基因，包括α 1b -肾上腺素受体（α1B-AR）、乙酰胆碱受体蛋白α链前体（ACHR）、camp依赖性3 ',5 ' -环磷酸二酯酶4D （PDE4D）、物质p受体（SPR）和ras相关蛋白RAB7。在健康对照中，这些基因均不受锂的调节。当我们比较这五个基因在双相情感障碍患者和健康对照者之间的表达时，在给药前，我们发现双相情感障碍患者的α1B-AR基因表达高于健康对照者。研究结果表明α1B-AR可能在锂离子处理的作用机制中发挥重要作用。
Lithium, a common drug for the treatment of bipolar disorder (BD), requires chronic administration to prevent recurrences of the illness. The necessity for long-term treatment suggests that changes in genes expression are involved in the mechanism of its action. We studied effects of lithium on gene expression in lymphoblasts from BD patients, all excellent responders to lithium prophylaxis. Gene expression was analyzed using cDNA arrays that included a total of 2400 cDNAs. We found that chronic lithium treatment at a therapeutically relevant concentration decreased the expression of seven genes in lymphoblasts from lithium responders. Five of these candidate lithium-regulated genes, including alpha1B-adrenoceptor (α1B-AR), acetylcholine receptor protein alpha chain precursor (ACHR), cAMP-dependent 3′,5′-cyclic phosphodiesterase 4D (PDE4D), substance-P receptor (SPR), and ras-related protein RAB7, were verified by Northern blotting analysis in lithium responders. None of these genes were regulated by lithium in healthy control subjects. When we compared the expression of these five genes between bipolar subjects and healthy control subjects at baseline, prior to lithium administration, we found that α1B-AR gene expression was higher in bipolar subjects than in healthy control subjects. Our findings indicate that α1B-AR may play an important role in the mechanism of action of lithium treatment.
大鼠大脑对锂加毛果芸香碱诱导的癫痫发作有明显的早期基因反应。
DOI：
10.1016/0169-328x(94)90281-x
发表时间：
1994
期刊：
Brain research. Molecular brain research
影响因子：
--
作者：
Williams,MB;Jope,RS
通讯作者：
Jope,RS