Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice

•Acute maternal fluoxetine treatment during pregnancy alters the fetal brain transcriptome.•Depletion of the microbiota modifies fetal brain responses to maternal fluoxetine treatment.•Opcml expression is regulated by maternal fluoxetine treatment and the maternal microbiota. Selective serotonin reu...

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Bibliographic Details
Published in:Behavioural brain research 2021-07, Vol.410, p.113353-113353, Article 113353
Main Authors: Vuong, Helen E., Coley, Elena J.L., Kazantsev, Maria, Cooke, Michaela E., Rendon, Tomiko K., Paramo, Jorge, Hsiao, Elaine Y.
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Cell Adhesion Molecules - drug effects
Disease Models, Animal
Embryo, Mammalian - drug effects
Female
Fluoxetine
Fluoxetine - administration & dosage
Fluoxetine - pharmacology
Gastrointestinal Microbiome - drug effects
GPI-Linked Proteins - drug effects
Male
Maternal microbiome
Mice
Mice, Inbred C57BL
Neurodevelopment
Opcml
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced
Selective Serotonin Reuptake Inhibitors - administration & dosage
Selective Serotonin Reuptake Inhibitors - pharmacology
SSRI
Transcriptome - drug effects
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Summary:•Acute maternal fluoxetine treatment during pregnancy alters the fetal brain transcriptome.•Depletion of the microbiota modifies fetal brain responses to maternal fluoxetine treatment.•Opcml expression is regulated by maternal fluoxetine treatment and the maternal microbiota. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment by women experiencing depression during pregnancy. However, the effects of maternal SSRI use on early offspring development remain poorly understood. Recent studies suggest that SSRIs can modify the gut microbiota and interact directly with particular gut bacteria, raising the question of whether the gut microbiome impacts host responses to SSRIs. In this study, we investigate effects of prenatal SSRI exposure on fetal neurodevelopment and further evaluate potential modulatory influences of the maternal gut microbiome. We demonstrate that maternal treatment with the SSRI fluoxetine induces widespread alterations in the fetal brain transcriptome during midgestation, including increases in the expression of genes relevant to synaptic organization and neuronal signaling and decreases in the expression of genes related to DNA replication and mitosis. Notably, maternal fluoxetine treatment from E7.5 to E14.5 has no overt effects on the composition of the maternal gut microbiota. However, maternal pretreatment with antibiotics to deplete the gut microbiome substantially modifies transcriptional responses of the fetal brain to maternal fluoxetine treatment. In particular, maternal fluoxetine treatment elevates localized expression of the opioid binding protein/cell adhesion molecule like gene Opcml in the fetal thalamus and lateral ganglionic eminence, which is prevented by maternal antibiotic treatment. Together, these findings reveal that maternal fluoxetine treatment alters gene expression in the fetal brain through pathways that are impacted, at least in part, by the presence of the maternal gut microbiota.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2021.113353