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

Korchynska, Solomiia ; Krassnitzer, Maria ; Malenczyk, Katarzyna ; Prasad, Rashmi B LU ; Tretiakov, Evgenii O ; Rehman, Sabah ; Cinquina, Valentina ; Gernedl, Victoria ; Farlik, Matthias and Petersen, Julian , et al. (2020) In EMBO Journal 39(1).
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... (More)

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 β 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.

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EMBO Journal
volume
39
issue
1
article number
e100882
publisher
Oxford University Press
external identifiers
  • scopus:85075401871
  • pmid:31750562
ISSN
1460-2075
DOI
10.15252/embj.2018100882
language
English
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yes
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©2019 The Authors. Published under the terms of the CC BY 4.0 license.
id
9b0d7b31-9dd3-4a70-9baa-096bdac57b22
date added to LUP
2019-11-22 10:34:21
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2020-01-15 09:56:29
@article{9b0d7b31-9dd3-4a70-9baa-096bdac57b22,
  abstract     = {<p>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 β 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.</p>},
  author       = {Korchynska, Solomiia and Krassnitzer, Maria and Malenczyk, Katarzyna and Prasad, Rashmi B and Tretiakov, Evgenii O and Rehman, Sabah and Cinquina, Valentina and Gernedl, Victoria and Farlik, Matthias and Petersen, Julian and Hannes, Sophia and Schachenhofer, Julia and Reisinger, Sonali N and Zambon, Alice and Asplund, Olof and Artner, Isabella and Keimpema, Erik and Lubec, Gert and Mulder, Jan and Bock, Christoph and Pollak, Daniela D and Romanov, Roman A and Pifl, Christian and Groop, Leif and Hökfelt, Tomas Gm and Harkany, Tibor},
  issn         = {1460-2075},
  language     = {eng},
  month        = {01},
  number       = {1},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants},
  url          = {http://dx.doi.org/10.15252/embj.2018100882},
  doi          = {10.15252/embj.2018100882},
  volume       = {39},
  year         = {2020},
}