liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide
Karolinska Institute, Sweden.
Karolinska Institute, Sweden; Centre Molecular Med, Sweden; Swedish Toxicol Science Research Centre Swetox, Sweden.
Douglas Mental Health University of Institute, Canada.
Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
Visa övriga samt affilieringar
2016 (Engelska)Ingår i: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, ISSN 0027-8424, Vol. 113, nr 52, s. E8472-E8481Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL(1-3), are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region- and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL(3) antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation.

Ort, förlag, år, upplaga, sidor
NATL ACAD SCIENCES , 2016. Vol. 113, nr 52, s. E8472-E8481
Nyckelord [en]
epigenetics; human postmortem brain; neuropeptides; stress; transmitter coexistence
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:liu:diva-134076DOI: 10.1073/pnas.1617824113ISI: 000391090800013PubMedID: 27940914OAI: oai:DiVA.org:liu-134076DiVA, id: diva2:1068910
Anmärkning

Funding Agencies|Swedish Research Council [04X-2887]; Swedish Brain Foundation; Karolinska Institutet; Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning (Formas); National Association for Research on Schizophrenia and Depression Distinguished Investigator Award; European Union Framework 6 Integrated Project New-Mood [LSHM-CT-2004-503474]; AFA Insurance; 5-y unrestricted Bristol-Myers-Squibb Grant in Neuroscience; Marianne and Marcus Wallenberg Foundation; Knut and Alice Wallenberg Foundation; Reseau Quebecois sur le Suicide, les Troubles de lHumeur et les Troubles Associes (FRQ-S); Platform Support Grant from Brain Canada; Magyar Tudomanyos Akademia (MTA)-Semmelweis Egyetem (SE)-Nemzeti Agykutatasi Program (NAP) B alprogram Genetic Brain Imaging Migraine Research Group through Kutatasi es Technologiai Innovacios Alap (KTIA) [KTIA_NAP_13-2-2015-0001]; NAP A-SE Research Group [KTIA_NAP_13-1-2013-0001, KTIA_13_NAP-A-II/14]; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group

Tillgänglig från: 2017-01-26 Skapad: 2017-01-22 Senast uppdaterad: 2018-01-13

Open Access i DiVA

fulltext(3655 kB)64 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 3655 kBChecksumma SHA-512
24491e8c169ab5d4651a07307124a0c7c56d8a2df07d29c07ef983bc93bc9a6812c31574d5b95a1d66cf4b59758436c8b19f0a27d6f8472df545c42f581f8979
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Sök vidare i DiVA

Av författaren/redaktören
Ihnatko, RobertTheodorsson, Elvar
Av organisationen
Avdelningen för mikrobiologi och molekylär medicinMedicinska fakultetenKlinisk kemi
Neurovetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 64 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 882 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf