Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.

Human endogenous retroviruses (HERVs) have been associated with various neurological and neuropsychiatric disorders. Transcripts and proteins of at least three HERV groups, HERV-W, ERV9 and HERV-K(HML-2) have been detected repeatedly in brain samples or cerebrospinal fluid of patients with schizophr...

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Autores principales: Olivia Diem, Marisa Schäffner, Wolfgang Seifarth, Christine Leib-Mösch
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:fa2a13a499fa45278c686b5865c562152021-11-18T07:30:26ZInfluence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.1932-620310.1371/journal.pone.0030054https://doaj.org/article/fa2a13a499fa45278c686b5865c562152012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253875/?tool=EBIhttps://doaj.org/toc/1932-6203Human endogenous retroviruses (HERVs) have been associated with various neurological and neuropsychiatric disorders. Transcripts and proteins of at least three HERV groups, HERV-W, ERV9 and HERV-K(HML-2) have been detected repeatedly in brain samples or cerebrospinal fluid of patients with schizophrenia suggesting that alterations in HERV activity may play a role in etiopathogenesis. Current therapies otherwise include neuroleptics and/or antidepressants that may induce epigenetic alterations and thus influence HERV expression. To investigate the effects of these drugs on HERV transcriptional activity, HERV expression profiles of a broad range of human brain cell lines treated with valproic acid (VPA), haloperidol, risperidone, and clozapine were analyzed using a retrovirus-specific microarray and qRT-PCR. Investigation of 52 HERV subgroups revealed upregulation of several class I and class II HERV elements by VPA in a dose-dependent manner. The strongest effect was observed on HERV-W and ERV9 groups in the human glioblastoma cell lines SK-N-SH and SK-N-MC, respectively. The transcript level of HERV-K(HML-2) elements was not influenced. Transcription of HERV-W, ERV9 and HERV-K(HML-2) taxa was further quantified in postmortem brain samples of patients with schizophrenia, bipolar disorders and a healthy control group with regard to their medication. Patients with schizophrenia showed a significantly higher HERV-W transcription associated with VPA treatment. However in case of ERV9, enhanced transcript levels could not be explained solely by VPA treatment, since a slight increase was also found in untreated patients compared to healthy controls. HERV-K(HML-2) elements appeared to be upregulated in some patients with bipolar disorders independent from medication. In conclusion, these results suggest that antipsychotic medication may contribute to increased expression of distinct HERV taxa in patients with neuropsychiatric diseases.Olivia DiemMarisa SchäffnerWolfgang SeifarthChristine Leib-MöschPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30054 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Olivia Diem
Marisa Schäffner
Wolfgang Seifarth
Christine Leib-Mösch
Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
description Human endogenous retroviruses (HERVs) have been associated with various neurological and neuropsychiatric disorders. Transcripts and proteins of at least three HERV groups, HERV-W, ERV9 and HERV-K(HML-2) have been detected repeatedly in brain samples or cerebrospinal fluid of patients with schizophrenia suggesting that alterations in HERV activity may play a role in etiopathogenesis. Current therapies otherwise include neuroleptics and/or antidepressants that may induce epigenetic alterations and thus influence HERV expression. To investigate the effects of these drugs on HERV transcriptional activity, HERV expression profiles of a broad range of human brain cell lines treated with valproic acid (VPA), haloperidol, risperidone, and clozapine were analyzed using a retrovirus-specific microarray and qRT-PCR. Investigation of 52 HERV subgroups revealed upregulation of several class I and class II HERV elements by VPA in a dose-dependent manner. The strongest effect was observed on HERV-W and ERV9 groups in the human glioblastoma cell lines SK-N-SH and SK-N-MC, respectively. The transcript level of HERV-K(HML-2) elements was not influenced. Transcription of HERV-W, ERV9 and HERV-K(HML-2) taxa was further quantified in postmortem brain samples of patients with schizophrenia, bipolar disorders and a healthy control group with regard to their medication. Patients with schizophrenia showed a significantly higher HERV-W transcription associated with VPA treatment. However in case of ERV9, enhanced transcript levels could not be explained solely by VPA treatment, since a slight increase was also found in untreated patients compared to healthy controls. HERV-K(HML-2) elements appeared to be upregulated in some patients with bipolar disorders independent from medication. In conclusion, these results suggest that antipsychotic medication may contribute to increased expression of distinct HERV taxa in patients with neuropsychiatric diseases.
format article
author Olivia Diem
Marisa Schäffner
Wolfgang Seifarth
Christine Leib-Mösch
author_facet Olivia Diem
Marisa Schäffner
Wolfgang Seifarth
Christine Leib-Mösch
author_sort Olivia Diem
title Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
title_short Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
title_full Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
title_fullStr Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
title_full_unstemmed Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells.
title_sort influence of antipsychotic drugs on human endogenous retrovirus (herv) transcription in brain cells.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/fa2a13a499fa45278c686b5865c56215
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