Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia.
Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia.
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DOI：
10.1016/j.psychres.2011.09.026
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发表时间：
2012-04-30
影响因子：
11.3
通讯作者：
Thomas, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Tang, Bin;Capitao, Cristina;Dean, Brian;Thomas, Elizabeth A.
我们以前已经确定了年龄对精神分裂症患者与正常对照组相比的全球大脑基因表达谱的差异影响。在这里，我们集中在与花生四烯酸相关的炎症通路相关的基因的年龄相关的影响。发表的微阵列表达数据的线性相关分析揭示了强大的年龄和细胞类型的特定影响的基因表达相关的花生四烯酸信号通路，不同的对照组相比，精神分裂症。使用实时qPCR分析，我们验证了年龄和疾病的影响花生四烯酸相关基因在一个大型队列的精神分裂症患者和匹配的对照组（n=76例）。我们发现，与匹配的正常对照组或年轻精神分裂症受试者（<40岁）相比，老年精神分裂症受试者（>40岁）中的加兰他汀-内过氧化物合酶1（PTGS 1; aka考克斯-1）和加兰他汀-内过氧化物受体3（PTGER 3）mRNA水平升高，加兰他汀-内过氧化物合酶2（PTGS 2; aka考克斯-2）mRNA水平降低。这些发现有助于积累证据，表明CNS中的炎症过程有助于精神分裂症的病理生理学，并进一步表明年龄可能是潜在使用抗炎治疗的重要因素。
We have previously identified differential effects of age on global brain gene expression profiles in subjects with schizophrenia compared to normal controls. Here, we have focused on age-related effects of genes associated with the arachidonic acid-related inflammation pathway. Linear correlation analysis of published microarray expression data reveal strong age- and cell-type specific-effects on the expression of genes related to the arachidonic acid signaling pathway, which differed in control subjects compared to those with schizophrenia. Using real-time qPCR analysis, we validated age- and disease-effects of arachidonic acid-related genes in a large cohort of subjects with schizophrenia and matched controls (n=76 subjects in total). We found that levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin-endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects with schizophrenia (>40 years of age) compared to matched normal controls or younger subjects with schizophrenia (<40 years of age). These findings contribute to the accumulating evidence suggesting that inflammatory processes in the CNS contribute to pathophysiology of schizophrenia and further suggest that age may be an important factor in the potential use of anti-inflammatory therapies.
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影响因子：
12.7
作者：
Steiner, Johann;Mawrin, Christian;Bogerts, Bernhard
通讯作者：
Bogerts, Bernhard
影响因子：
2.5
作者：
Bayer, TA;Buslei, R;Falkai, P
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Falkai, P
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Ross, BM;Turenne, S;Kish, SJ
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Kish, SJ
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作者：
Rapaport, MH;Delrahim, KK;Dolnak, D
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Dolnak, D
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17.7
作者：
Müller, N;Riedel, M;Schwarz, MJ
通讯作者：
Schwarz, MJ