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PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2014 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1839, no 11, 1226-1232 p.Article in journal (Refereed) Published
Abstract [en]

The dynorphin kappa-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.

Place, publisher, year, edition, pages
2014. Vol. 1839, no 11, 1226-1232 p.
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Medical Bioscience
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URN: urn:nbn:se:uu:diva-239370DOI: 10.1016/j.bbagrm.2014.09.001ISI: 000345490400018PubMedID: 25220237OAI: oai:DiVA.org:uu-239370DiVA: diva2:774845
Available from: 2014-12-29 Created: 2014-12-22 Last updated: 2017-12-05Bibliographically approved

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Bazov, IgorBakalkin, Georgy

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