Dataset of histone H3K4me2 modified genes in the liver of female Sprague-Dawleyrats with chronic antipsychotic drugs of olanzapine or clozapine
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1215965 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32131331.fastq.gz | Fastqsanger.gz | |||
| SRR32131332.fastq.gz | Fastqsanger.gz | |||
| SRR32131333.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
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Project description:Epigenetic histone modificationshave been found to be associated with the development of metabolic disorders.However,the potential contribution of these modifications to metabolic disturbances induced by chronic treatment with second-generation antipsychotic drugs (SGAs) remains unclear. This study presents chromatin immunoprecipitation (ChIP) data on H3K4me methylation in hepatic tissue of rats treated with olanzapine or clozapine for 9 weeks.This dataset provides a comprehensive view of the effects of SGAs on H3K4me methylation in an animal model, offering new insights into the epigenetic mechanisms underlying SGAs-induced metabolic side effects.
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Project description:Antipsychotic drugs are commonly used to treat psychosis, mood disorders, and anxiety. While there is indirect evidence that some component of the antipsychotic effect of these drugs may involve modulation of dopamine transmission, their mechanism of action is poorly understood. We hypothesized that antipsychotic drugs mediate their effects via epigenetic modulation. Here we tested the effect of an antipsychotic, olanzapine, on the methylation status of genes following chronic treatment. These effects have been revealed through significantly increased (p<0.01) DNA methylation of genes involved in dopaminergic and non-dopaminergic pathways including the glutamatergic, GABAergic, cholinergic, neuregulin and ErbB signaling pathways. The affected genes included GLS in hippocampus, NR1 in cerebellum and GLUD1 and NR2B in liver. Further, from a set of genes in the 22q11.2 micro-deletions that has been previously implicated in psychosis, 22 genes showed increased methylation following olanzapine treatment. Ingenuity Pathway Analysis (IPA) revealed that chronic olanzapine treatment significantly affected several important pathways such as CREB and CDK5 signaling (p=1.4E-05). Also, DNA replication, recombination and repair, cellular movement and cell cycle have been identified as the top networks affected by olanzapine. The results suggest that these downstream effects, aside from D2 blockade, may play a critical role in the biological actions of antipsychotics. These include altered expressions of relevant genes involved in GABAergic, glutamatergic, cholinergic, neuregulin and ErbB signaling pathways. Epigenetic mechanisms involving changes in DNA methylation could, therefore, explain the delay and individualized non-specificity of biological effects of olanzapine. The results also suggest that DNA methylation may play a role in the process of therapeutic efficacy of olanzapine by altering the transcriptome via tissue-specific methylation of genes involved in schizophrenia signaling pathways.
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