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

A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior

“…In addition, stress loading is often performed before pregnancy 18 , 25 because physical stress loading may be severe during pregnancy. A recent study showed that isolated mice exhibited increased depression-like behavior than group-housing mice 26 , supporting the notion that psychological stress can induce depression even without physical stress loading.…”

Mouse Model of Weak Depression Exhibiting Suppressed cAMP Signaling in the Amygdala, Lower Lipid Catabolism in Liver, and Correlated Gut Microbiota

“…For example, Xie et al (2019) reported an ameliorating effect of Lactobacillus reuteri on depressive behavior and its correlation to serotonin, whose precursor, tryptophan can be metabolized by Kynu and Nampt into NAD. More importantly, Scarborough et al (2021) investigated the role of serotonin in the social isolation model using serotonin reuptake inhibitor, fluoxetine (FLX). They found that FLX treatment was effective to prevent anxiety-related behaviors both in the isolated generation (dams) and in their offspring.…”

A comprehensive approach to modeling maternal immune activation in rodents

“…Two prevailing methods of imposing social stress on laboratory housed rodents that are arguably most related to aspects of human social behavior, are the social isolation and social instability stress paradigm (Table 3). One study modeled maternal depression in mice by incorporating social isolation both before and during gestation; concomitantly with antidepressant use (fluoxetine) (Scarborough et al, 2021). The social isolation paradigm per se, is not what makes this study unique.…”

“…Environmental perturbations during pregnancy that result in either acute or chronic instances of inflammation in the human condition have been shown to include, dietary composition, frequency of exercise, adequate sleep, socioeconomic status, stress, exposure to pollutants, and the gut microbiome (Han et al, 2021a). The all-inclusive contribution of these factors has yet to be explored in an MIA rodent model but at present, there are reports from those who have explored the role of the maternal microbiome (Kim et al, 2017;Lammert et al, 2018), social stress or social isolation rearing (Vallée et al, 1997;Scarborough et al, 2021) and a maternal highfat diet (Bordeleau et al, 2020) on the resulting molecular and/or behavioral alterations in developing offspring (the use of environmental gestational stress paradigms in rodents are extensively reviewed here: Brunton, 2013;Weinstock, 2017;Van den Bergh et al, 2020).…”