The expression of the transcription factor FEV in adult human brain and its association with affective disorders.

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.

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