Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

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Korchynska , S , Krassnitzer , M , Malenczyk , K , Prasad , R B , Tretiakov , E O , Rehman , S , Cinquina , V , Gernedl , V , Farlik , M , Petersen , J , Hannes , S , Schachenhofer , J , Reisinger , S N , Zambon , A , Asplund , O , Artner , I , Keimpema , E , Lubec , G , Mulder , J , Bock , C , Pollak , D D , Romanov , R A , Pifl , C , Groop , L , Hokfelt , T G M & Harkany , T 2020 , ' Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants ' , EMBO Journal , vol. 39 , no. 1 , 100882 .

Title: Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants
Author: Korchynska, Solomiia; Krassnitzer, Maria; Malenczyk, Katarzyna; Prasad, Rashmi B.; Tretiakov, Evgenii O.; Rehman, Sabah; Cinquina, Valentina; Gernedl, Victoria; Farlik, Matthias; Petersen, Julian; Hannes, Sophia; Schachenhofer, Julia; Reisinger, Sonali N.; Zambon, Alice; Asplund, Olof; Artner, Isabella; Keimpema, Erik; Lubec, Gert; Mulder, Jan; Bock, Christoph; Pollak, Daniela D.; Romanov, Roman A.; Pifl, Christian; Groop, Leif; Hokfelt, Tomas G. M.; Harkany, Tibor
Contributor organization: Centre of Excellence in Complex Disease Genetics
HUS Abdominal Center
Institute for Molecular Medicine Finland
University of Helsinki
Date: 2020-01-02
Language: eng
Number of pages: 19
Belongs to series: EMBO Journal
ISSN: 0261-4189
Abstract: Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic beta cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.
Subject: diabetes
beta cell
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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