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A novel murine model to study the impact of maternal depression and antidepressant treatment on biobehavioral functions in the offspring


Scarborough, Joseph; Mueller, Flavia S; Weber-Stadlbauer, Ulrike; Mattei, Daniele; Opitz, Lennart; Cattaneo, Annamaria; Richetto, Juliet (2021). A novel murine model to study the impact of maternal depression and antidepressant treatment on biobehavioral functions in the offspring. Molecular Psychiatry, 26(11):6756-6772.

Abstract

Antenatal psychopathology negatively affects obstetric outcomes and exerts long-term consequences on the offspring's wellbeing and mental health. However, the precise mechanisms underlying these associations remain largely unknown. Here, we present a novel model system in mice that allows for experimental investigations into the effects of antenatal depression-like psychopathology and for evaluating the influence of maternal pharmacological treatments on long-term outcomes in the offspring. This model system in based on rearing nulliparous female mice in social isolation prior to mating, leading to a depressive-like state that is initiated before and continued throughout pregnancy. Using this model, we show that the maternal depressive-like state induced by social isolation can be partially rescued by chronic treatment with the selective serotonin reuptake inhibitor, fluoxetine (FLX). Moreover, we identify numerous and partly sex-dependent behavioral and molecular abnormalities, including increased anxiety-like behavior, cognitive impairments and alterations of the amygdalar transcriptome, in offspring born to socially isolated mothers relative to offspring born to mothers that were maintained in social groups prior to conception. We also found that maternal FLX treatment was effective in preventing some of the behavioral and molecular abnormalities emerging in offspring born to socially isolated mothers. Taken together, our findings suggest that the presence of a depressive-like state during preconception and pregnancy has sex-dependent consequences on brain and behavioral functions in the offspring. At the same time, our study highlights that FLX treatment in dams with a depression-like state can prevent abnormal behavioral development in the offspring.

Abstract

Antenatal psychopathology negatively affects obstetric outcomes and exerts long-term consequences on the offspring's wellbeing and mental health. However, the precise mechanisms underlying these associations remain largely unknown. Here, we present a novel model system in mice that allows for experimental investigations into the effects of antenatal depression-like psychopathology and for evaluating the influence of maternal pharmacological treatments on long-term outcomes in the offspring. This model system in based on rearing nulliparous female mice in social isolation prior to mating, leading to a depressive-like state that is initiated before and continued throughout pregnancy. Using this model, we show that the maternal depressive-like state induced by social isolation can be partially rescued by chronic treatment with the selective serotonin reuptake inhibitor, fluoxetine (FLX). Moreover, we identify numerous and partly sex-dependent behavioral and molecular abnormalities, including increased anxiety-like behavior, cognitive impairments and alterations of the amygdalar transcriptome, in offspring born to socially isolated mothers relative to offspring born to mothers that were maintained in social groups prior to conception. We also found that maternal FLX treatment was effective in preventing some of the behavioral and molecular abnormalities emerging in offspring born to socially isolated mothers. Taken together, our findings suggest that the presence of a depressive-like state during preconception and pregnancy has sex-dependent consequences on brain and behavioral functions in the offspring. At the same time, our study highlights that FLX treatment in dams with a depression-like state can prevent abnormal behavioral development in the offspring.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Pharmacology and Toxicology
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Biology
Life Sciences > Cellular and Molecular Neuroscience
Health Sciences > Psychiatry and Mental Health
Language:English
Date:17 May 2021
Deposited On:08 Feb 2022 17:27
Last Modified:26 Jun 2024 01:46
Publisher:Nature Publishing Group
ISSN:1359-4184
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41380-021-01145-7
PubMed ID:34002019
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)