Molecular and Clinical Psychobiology, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany.
J Neural Transm (Vienna). 2010 Jul;117(7):831-6. doi: 10.1007/s00702-010-0405-8. Epub 2010 May 18.
A wide range of physiological processes and neuronal functioning is modulated by the serotonergic system. Serotonin (5-HT) plays an important role during early brain development. Moreover, dysfunction of the 5-HT system is implicated in psychiatric disorders, especially in affective disorders. Little is known, however, about the transcriptional mechanisms leading to a functional 5-HT system in humans. The Fifth Ewing Variant (FEV), an E-twenty-six (ETS) transcription factor, is assumed to be involved in the transcription of gene(s) in the serotonergic pathway and to play a role in early brain development. To investigate its specificity, we performed an expression analysis of FEV in different human brain regions utilizing quantitative real-time polymerase chain reaction. Our results demonstrate that FEV is not exclusively expressed in serotonergic neurons, but, on the contrary, also in several non-serotonergic brain regions such as locus coeruleus, caudate nucleus and putamen. In the latter two regions, FEV expression levels actually were higher when compared with the pons and the medulla oblongata, which contain the raphe nuclei. Additionally, we examined whether genetic variance in the FEV gene contributes to the susceptibility towards affective disorders. Direct re-sequencing, however, did not provide evidence for FEV mutations in patients, and neither were non-coding single nucleotide polymorphisms associated with disease. FEV therefore might not account for the genetic risk towards depression or bipolar disorder. Furthermore, the specificity of FEV for the serotonergic system should be reconsidered.
5-羟色胺（5-HT）系统调节着广泛的生理过程和神经元功能。5-HT 在大脑早期发育中起着重要作用。此外，5-HT 系统功能障碍与精神疾病有关，尤其是情感障碍。然而，人们对导致人类功能性 5-HT 系统的转录机制知之甚少。第五个 Ewing 变体（FEV）是一个 E-二十六个（ETS）转录因子，据信参与 5-HT 途径中基因的转录，并在大脑早期发育中发挥作用。为了研究其特异性，我们利用定量实时聚合酶链反应（PCR）分析了 FEV 在不同人脑区域的表达。我们的结果表明，FEV 并非仅在 5-HT 神经元中表达，而是相反，也在几个非 5-HT 脑区如蓝斑、尾状核和壳核中表达。在后两个区域，FEV 的表达水平实际上高于包含中缝核的脑桥和延髓。此外，我们还研究了 FEV 基因的遗传变异是否导致易感性情感障碍。然而，直接重测序并未在患者中提供 FEV 突变的证据，也没有非编码单核苷酸多态性与疾病相关。因此，FEV 可能不能解释抑郁或双相情感障碍的遗传风险。此外，应该重新考虑 FEV 对 5-HT 系统的特异性。
