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  • Lupu, DianaDepartment of Toxicology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Unit Toxicol Sci, Karolinska Institute, Södertälje, Sweden (author)

Fluoxetine Affects Differentiation of Midbrain Dopaminergic Neurons In Vitro

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-08-16
  • New York :American Society for Pharmacology and Experimental Therapeutics,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-83056
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-83056URI
  • https://doi.org/10.1124/mol.118.112342DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-161025URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:139236444URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • Ytterligare forskningsfinansiär: Emil and Wera Cornell's research foundation
  • Recent meta-analyses found an association between prenatal exposure to the antidepressant fluoxetine (FLX) and an increased risk of autism in children. This developmental disorder has been related to dysfunctions in the brains' rewards circuitry, which, in turn, has been linked to dysfunctions in dopaminergic (DA) signaling. The present study investigated if FLX affects processes involved in dopaminergic neuronal differentiation. Mouse neuronal precursors were differentiated into midbrain dopaminergic precursor cells (mDPCs) and concomitantly exposed to clinically relevant doses of FLX. Subsequently, dopaminergic precursors were evaluated for expression of differentiation and stemness markers using quantitative polymerase chain reaction. FLX treatment led to increases in early regional specification markers orthodenticle homeobox 2 (Otx2) and homeobox engrailed-1 and -2 (En1 and En2). On the other hand, two transcription factors essential for midbrain dopaminergic (mDA) neurogenesis, LIM homeobox transcription factor 1 alpha (Lmx1a) and paired-like homeodomain transcription factor 3 (Pitx3) were downregulated by FLX treatment. The stemness marker nestin (Nes) was increased, whereas the neuronal differentiation marker beta 3-tubulin (Tubb3) decreased. Additionally, we observed that FLX modulates the expression of several genes associated with autism spectrum disorder and downregulates the estrogen receptors (ERs) alpha and beta. Further investigations using ER beta knockout (BERKO) mDPCs showed that FLX had no or even opposite effects on several of the genes analyzed. These findings suggest that FLX affects differentiation of the dopaminergic system by increasing production of dopaminergic precursors, yet decreasing their maturation, partly via interference with the estrogen system.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Varshney, Mukesh K.Karolinska Institutet (author)
  • Mucs, DanielKarolinska Institutet (author)
  • Inzunza, JoseKarolinska Institutet (author)
  • Norinder, Ulf,1956-Stockholms universitet,Institutionen för data- och systemvetenskap,Swetox, Karolinska Institutet, Sweden(Swepub:su)unori (author)
  • Loghin, FeliciaDepartment of Toxicology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania (author)
  • Nalvarte, IvanKarolinska Institutet (author)
  • Ruegg, JoelleKarolinska Institutet (author)
  • Karolinska InstitutetDepartment of Toxicology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Unit Toxicol Sci, Karolinska Institute, Södertälje, Sweden (creator_code:org_t)

Related titles

  • In:Molecular PharmacologyNew York : American Society for Pharmacology and Experimental Therapeutics94:4, s. 1220-12310026-895X1521-0111

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