title: PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.
abstract: The dynorphin κ-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.
authors.affiliation: Integrative Neuroscience Section, Integrative Neuroscience Research Branch, NIDA-IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224, USA; Department of Clinical Neuroscience, Karolinska Institutet, Cell and Molecular Medicine, L8:01, 17176 Stockholm, Sweden; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, Box 591, Husargatan 3, 751 24 Uppsala, Sweden. Electronic address: richard.henriksson@farmbio.uu.se.
authors.forename: Richard
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: Cellular Neurophysiology Section, Cellular Neurobiology Research Branch, NIDA-IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Bäckman
authors.affiliation: Neural Protection and Regeneration Section, Molecular Neuropsychiatry Research Branch, NIDA-IRP, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, Box 591, Husargatan 3, 751 24 Uppsala, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Kadyrova
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, Box 591, Husargatan 3, 751 24 Uppsala, Sweden.
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.affiliation: Integrative Neuroscience Section, Integrative Neuroscience Research Branch, NIDA-IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224, USA.
authors.forename: Toni S
authors.initials: TS
authors.lastname: Shippenberg
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, Box 591, Husargatan 3, 751 24 Uppsala, Sweden.
authors.forename: Georgy
authors.initials: G
authors.lastname: Bakalkin
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D004745:Enkephalins; D035683:MicroRNAs; D011498:Protein Precursors; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C541874:MIRN92 microRNA, human; C033660:preproenkephalin
keywords: MIR-9; NRSF; PDYN; Prefrontal cortex; REST; SH-SY5Y cell