Regulation of alternative gene expression in the mouse striatum in response to cocaine

• Autorzy: Zygmunt M. , Rodriguez-Parkitna J. , Golda S. , Piechota M. , Ficek J. , Korostynski M.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Cocaine is a potent psychostimulant that increases levels of striatal dopamine and activates neuronal circuits controlling motivation and reward-based learning. Transcriptional response to cocaine includes expression of alternative gene isoforms and splicing variants. Unraveling the regulatory mechanisms that are involved in selection of active transcription start and termination sites provides novel insight into molecular basis of drug-induced brain plasticity. METHODS: We used next-generation sequencing (RNA-seq) to comprehensively map expression of genesin the mouse striatum. Total RNA and small RNA resequencing was performed in samples collected 1 h after acute treatment with 25 mg/kg cocaine. To identify transcripts responsive to drug treatment we used Tophat read-mapper and Cufflinks algorithm for FPKM quantification. The seqinterpreter online tool was used to search for key regulatory factors that control alternative gene transcription in the brain (http://seqinterpreter.cremag.org). RESULTS: In addition to increased expression of activity-regulated genes, different types of cocaine-inducible splicing variants and transcript biotypes were identified. Examples of different modalities of gene expression include alternative first exon (e.g. Stxbp1), alternative last exon (Hsph1), intron retention (Dnajb5), long noncoding RNA (Gm13889) and small RNA (Mir92b and Mir130a). In order to investigate neuron-type specificity of gene expression we have used fluorescence-activated cell sorting to isolate genetically labeled dopamine receptor 1 expressing neurons. CONCLUSIONS: Our results provide a comprehensive assessment of neuronal activity-induced gene expression at the level of individual transcriptional units rather than whole genes. Further experiments will explore differences in activity-regulated gene expression in discrete neuron types, i.e. the D1 or D2 expressing medium spiny neurons of the striatum. This work was supported by NCN grant SONATA 2011/03/D/ NZ3/01686.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S65

Twórcy

autor

Zygmunt M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Rodriguez-Parkitna J.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Golda S.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Piechota M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Ficek J.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Korostynski M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland