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  • Bazov, Igor,1973-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden (author)

Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-06-20
  • NATURE PUBLISHING GROUP,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-358683
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-358683URI
  • https://doi.org/10.1038/s41398-017-0075-5DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-82991URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit. We addressed this hypothesis by comparing the expression levels and co-expression (transcriptionally coordinated) patterns of PDYN and KOR (OPRK1) genes in dorsolateral prefrontal cortex (dlPFC) between human alcoholics and controls. Postmortem brain specimens of 53 alcoholics and 55 controls were analyzed. PDYN was found to be downregulated in dlPFC of alcoholics, while OPRK1 transcription was not altered. PDYN downregulation was confined to subgroup of subjects carrying C, a high-risk allele of PDYN promoter SNP rs1997794 associated with alcoholism. Changes in PDYN expression did not depend on the decline in neuronal proportion in alcoholics, and thereby may be attributed to transcriptional adaptations in alcoholic brain. Absolute expression levels of PDYN were lower compared to those of OPRK1, suggesting that PDYN expression is a limiting factor in the DYN/KOR signaling, and that the PDYN downregulation diminishes efficacy of DYN/KOR signaling in dlPFC of human alcoholics. The overall outcome of the DYN/KOR downregulation may be disinhibition of neurotransmission, which when overactivated could contribute to formation of alcohol-related behavior.

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  • Sarkisyan, DaniilUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)dansa302 (author)
  • Kononenko, OlgaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)olgko690 (author)
  • Watanabe, HiroyukiUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)hirwa520 (author)
  • Karpyak, Victor M.Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN 55905 USA,Mayo Clinic College of Medicine, Rochester, USA (author)
  • Yakovleva, TatianaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)tatia678 (author)
  • Bakalkin, GeorgyUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)gueba200 (author)
  • Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Related titles

  • In:Translational Psychiatry: NATURE PUBLISHING GROUP82158-3188

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