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Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions


Giovanoli, Sandra; Werge, Thomas M; Mortensen, Preben B; Didriksen, Michael; Meyer, Urs (2019). Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions. Neuropsychopharmacology, 44(4):703-710.

Abstract

15q13.3 microdeletion is one of several gene copy number variants (CNVs) conferring increased risk of psychiatric and neurological disorders. This microdeletion gives rise to a variable spectrum of pathological phenotypes, ranging from asymptomatic to severe clinical outcomes. The reasons for these varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous deletion of the orthologous region of 15q13.3, the present study examined whether exposure to stressful life events might interact with hemizygous 15q13.3 microdeletion in the development of behavioral dysfunctions. We show that hemizygous 15q13.3 microdeletion alone induces only limited effects on adult behaviors, but when combined with psychological stress in pubescence (postnatal days 30-40), it impairs sensorimotor gating and increases the sensitivity to the psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence (postnatal days 50-60) did not induce similar interactions with 15q13.3 microdeletion, but led to impaired emotional learning and memory and social behavior regardless of the genetic background. The present study provides the first evidence for interactive effects between hemizygous 15q13.3 microdeletion and exposure to stressful life events, and at the same time, it emphasizes an important influence of the precise timing of postnatal stress exposure in these interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act as a "disease primer" that increases the carrier's vulnerability to the detrimental effects of peripubertal stress exposure on adult behaviors.

Abstract

15q13.3 microdeletion is one of several gene copy number variants (CNVs) conferring increased risk of psychiatric and neurological disorders. This microdeletion gives rise to a variable spectrum of pathological phenotypes, ranging from asymptomatic to severe clinical outcomes. The reasons for these varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous deletion of the orthologous region of 15q13.3, the present study examined whether exposure to stressful life events might interact with hemizygous 15q13.3 microdeletion in the development of behavioral dysfunctions. We show that hemizygous 15q13.3 microdeletion alone induces only limited effects on adult behaviors, but when combined with psychological stress in pubescence (postnatal days 30-40), it impairs sensorimotor gating and increases the sensitivity to the psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence (postnatal days 50-60) did not induce similar interactions with 15q13.3 microdeletion, but led to impaired emotional learning and memory and social behavior regardless of the genetic background. The present study provides the first evidence for interactive effects between hemizygous 15q13.3 microdeletion and exposure to stressful life events, and at the same time, it emphasizes an important influence of the precise timing of postnatal stress exposure in these interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act as a "disease primer" that increases the carrier's vulnerability to the detrimental effects of peripubertal stress exposure on adult behaviors.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Pharmacology, Psychiatry and Mental health
Language:English
Date:1 March 2019
Deposited On:24 Jan 2019 17:08
Last Modified:13 Feb 2019 02:07
Publisher:Nature Publishing Group
ISSN:0893-133X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41386-018-0189-3
PubMed ID:30188511
Project Information:
  • : FunderSNSF
  • : Grant ID310030_169544
  • : Project TitleEpigenetic and Transgenerational Mechanisms in Infection-Mediated Neurodevelopmental Disorders

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