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Expression of alternatively spliced variants of the Dclk1 gene is regulated by psychotropic drugs

Overview of attention for article published in BMC Neuroscience, September 2018
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Title
Expression of alternatively spliced variants of the Dclk1 gene is regulated by psychotropic drugs
Published in
BMC Neuroscience, September 2018
DOI 10.1186/s12868-018-0458-4
Pubmed ID
Authors

Magdalena Zygmunt, Dżesika Hoinkis, Jacek Hajto, Marcin Piechota, Bożena Skupień-Rabian, Urszula Jankowska, Sylwia Kędracka-Krok, Jan Rodriguez Parkitna, Michał Korostyński

Abstract

The long-term effects of psychotropic drugs are associated with the reversal of disease-related alterations through the reorganization and normalization of neuronal connections. Molecular factors that trigger drug-induced brain plasticity remain only partly understood. Doublecortin-like kinase 1 (Dclk1) possesses microtubule-polymerizing activity during synaptic plasticity and neurogenesis. However, the Dclk1 gene shows a complex profile of transcriptional regulation, with two alternative promoters and exon splicing patterns that suggest the expression of multiple isoforms with different kinase activities. Here, we applied next-generation sequencing to analyze changes in the expression of Dclk1 gene isoforms in the brain in response to several psychoactive drugs with diverse pharmacological mechanisms of action. We used bioinformatics tools to define the range and levels of Dclk1 transcriptional regulation in the mouse nucleus accumbens and prefrontal cortex. We also sought to investigate the presence of DCLK1-derived peptides using mass spectrometry. We detected 15 transcripts expressed from the Dclk1 locus (FPKM > 1), including 2 drug-regulated variants (fold change > 2). Drugs that act on serotonin receptors (5-HT2A/C) regulate a subset of Dclk1 isoforms in a brain-region-specific manner. The strongest influence was observed for the mianserin-induced expression of an isoform with intron retention. The drug-activated expression of novel alternative Dclk1 isoforms was validated using qPCR. The drug-regulated isoform contains genetic variants of DCLK1 that have been previously associated with schizophrenia and hyperactivity disorder in humans. We identified a short peptide that might originate from the novel DCLK1 protein product. Moreover, protein domains encoded by the regulated variant indicate their potential involvement in the negative regulation of the canonical DCLK1 protein. In summary, we identified novel isoforms of the neuroplasticity-related gene Dclk1 that are expressed in the brain in response to psychotropic drug treatments.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 3 16%
Student > Ph. D. Student 3 16%
Student > Master 3 16%
Researcher 2 11%
Student > Bachelor 2 11%
Other 3 16%
Unknown 3 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 26%
Neuroscience 4 21%
Agricultural and Biological Sciences 3 16%
Medicine and Dentistry 1 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Other 0 0%
Unknown 5 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 September 2018.
All research outputs
#10,306,257
of 13,511,578 outputs
Outputs from BMC Neuroscience
#671
of 1,039 outputs
Outputs of similar age
#183,312
of 264,545 outputs
Outputs of similar age from BMC Neuroscience
#1
of 3 outputs
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