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Genomic response of neuronal cell to external stimuli includes expression of specific transcript isoforms, that use alternative transcription start sites and polyadenylation signals. We applied microarray profiling (Illumina Mouse WG-6) and next-generation sequencing (SOLID 5500xl) to screen for drug-induced activitydependent transcriptional events in the C57BL/6J mouse striatum. We compared effects on gene expression induced by psychoactive drugs with diverse neuropharmacological mechanisms of action (antidepressants, antipsychotics, anxiolytics, psychostimulants and opiods). Using whole-genome approach we identified a pool of transcripts that are regulated by the psychotropic drugs in mouse striatum (317 transcripts). We found that drug-responsive transcripts are organized into three main co-regulated gene expression networks. Furthermore, using Bowtie read aligner and Cufflinks algorithm we identified specific gene isoforms responsive to drug treatment. 58% among the drug-regulated transcripts were defined as alternative transcription events. To search for transcriptional factors that control alternative gene transcription in the brain we developed seqinterpreter web-based tool (http:// seqinterpreter.cremag.org). We found SRF, NPAS4 and GR as candidate regulatory factors. The complex program of regulation in gene transcription may further impact long-lasting alterations in brain function.
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p.42
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- Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
autor
- Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
autor
- Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
autor
- Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
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bwmeta1.element.agro-3069f387-ca25-4930-85e9-bbcfb9832492