Costa Marta, Squassina Alessio, Piras Ignazio Stefano, Pisanu Claudia, Congiu Donatella, Niola Paola, Angius Andrea, Chillotti Caterina, Ardau Raffaella, Severino Giovanni, Stochino Erminia, Deidda Arianna, Persico Antonio M, Alda Martin, Del Zompo Maria
Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Sp 8 Sestu-Monserrato, Km 0.700, 09042, Monserrato, Cagliari, Italy.
J Mol Neurosci. 2015 Jul;56(3):688-95. doi: 10.1007/s12031-015-0567-9. Epub 2015 Apr 28.
Bipolar disorder (BD) and cluster headache (CH) are distinct conditions with important similarities such as a temporal pattern of disturbances, dysregulation of the sleep-wake cycle, and response to lithium treatment in a proportion of patients. Aiming to identify common transcription signatures in these two disorders, we carried out an exploratory microarray gene expression analysis in lymphoblasts from 8 CH and 10 BD I patients selected for positive response to lithium and 10 healthy controls (CO). Gene expression levels of BD and CH were compared with CO to create two lists of differentially expressed genes. We then matched the two lists and focus on genes showing statistically significant difference and same change direction in both disorders. RNA binding motif protein 3 (RBM3) was the most significantly altered gene in the list (3.17 × 10(-13) in BD, 9.44 × 10(-14) in CH). Pathway analysis identified protein processing in endoplasmic reticulum as the most significantly enriched. For validation with quantitative reverse transcription PCR (qRT-PCR) using the same samples, we selected seven genes. Among these, we were able to validate the RBM3, nuclear receptor subfamily 1, group D, member 1 (NR1D1), and tryptophan hydroxylase 1 (TPH1). These genes encode for elements involved in circadian rhythm regulation (RBM3 and NR1D1) and in serotonin synthesis (TPH1), processes previously involved in both disorders, and in the mechanism of action of lithium.
双相情感障碍（BD）和丛集性头痛（CH）是两种不同的疾病，但存在重要的相似之处，如紊乱的时间模式、睡眠-觉醒周期失调以及部分患者对锂治疗有反应。为了确定这两种疾病中共同的转录特征，我们对8名丛集性头痛患者、10名对锂治疗有阳性反应的双相I型障碍患者以及10名健康对照者（CO）的淋巴细胞进行了探索性微阵列基因表达分析。将双相情感障碍和丛集性头痛的基因表达水平与健康对照者进行比较，以创建两个差异表达基因列表。然后我们匹配这两个列表，并关注在两种疾病中显示出统计学显著差异且变化方向相同的基因。RNA结合基序蛋白3（RBM3）是列表中变化最显著的基因（双相情感障碍中为3.17×10⁻¹³，丛集性头痛中为9.44×10⁻¹⁴）。通路分析确定内质网中的蛋白质加工是最显著富集的通路。为了使用相同样本通过定量逆转录PCR（qRT-PCR）进行验证，我们选择了7个基因。其中，我们能够验证RBM3、核受体亚家族1 D组成员1（NR1D1）和色氨酸羟化酶1（TPH1）。这些基因编码参与昼夜节律调节的元件（RBM3和NR1D1）以及血清素合成相关元件（TPH1），这些过程先前在这两种疾病以及锂的作用机制中均有涉及。
