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Regulation of Human Endogenous Retrovirus (HERV) expression in human brain cells.
Vortrag: 4th European Congress of Virology, 07-11 April 2010, Cernobbio, Como Lake, Italy. (2010)
The expression profiles of a broad range of HERVs were analyzed in brain samples from patients with schizophrenia, bipolar disorders and healthy controls using a retrovirus specific microarray. Remarkably, upregulation of HERV-K(HML-2) elements was found to be significantly prevalent in both, bipolar disorder- and schizophrenia-associated samples, suggesting a potential association with disease. Therefore, the methylation status of HERV-K(HML-2) loci active in patient samples was investigated in various human brain cells. Preliminary results indicate a correlation between DNA demethylation and transcriptional activity of HERV-K (HML-2) loci. In addition, we have investigated a potential influence of psychiatric medication on HERV transcription activity, since the majority of patients were treated with neuroleptica and/or antidepressants. Various cell lines derived from human brain (astrocytes and neuronal cells) were treated with different antipsychotic drugs, such as valproic acid, haloperidol, risperidone and clozapine. The drugs were used in non-cytotoxic concentrations. Alterations of HERV expression patterns were monitored with the retrovirus-specific microarray. All medications tested so far showed an influence on expression of at least some HERV families. A dose-dependent upregulation of transcriptional activity after treatment with valproic acid, haloperidol and risperidone was observed for several class I (HERV-Fb, HERV-W, ERV9) and class II HERVs (HERV-KC4). Valproic acid additionally showed an increased activity of HML-3 (class II HERV). Medication-dependent differences of HERV activity were validated by QRT-PCR. Furthermore, preliminary data suggest that members of the HML-2 family are not influenced. Thus, the differential HERV-K10 activity detected in brain samples of patients may rather relate to the disease than to psychiatric medication.
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Publikationstyp Sonstiges: Vortrag
Konferenztitel 4th European Congress of Virology
Konferzenzdatum 07-11 April 2010
Konferenzort Cernobbio, Como Lake, Italy
Institut(e) Institute of Virology (VIRO)