RT Journal Article
SR Electronic
T1 Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.26.221648
DO 10.1101/2020.07.26.221648
A1 Anouschka S. Ramsteijn
A1 Rikst Nynke Verkaik-Schakel
A1 Danielle J. Houwing
A1 Torsten Plösch
A1 Jocelien D.A. Olivier
YR 2020
UL http://biorxiv.org/content/early/2020/07/26/2020.07.26.221648.abstract
AB Many pregnant women experience symptoms of depression, and are often treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine. In utero exposure to SSRIs and maternal depressive symptoms is associated with sex-specific effects on the brain and behavior. However, knowledge about the neurobiological mechanisms underlying these sex differences is limited. In addition, most animal research into developmental SSRI exposure neglects the influence of maternal adversity. Therefore, we used a rat model relevant to depression to investigate the molecular effects of perinatal fluoxetine exposure in male and female juvenile offspring. We performed RNA sequencing and targeted DNA methylation analyses on the prefrontal cortex and basolateral amygdala; key regions of the corticolimbic circuit. Perinatal fluoxetine enhanced myelin-related gene expression in the prefrontal cortex, while inhibiting it in the basolateral amygdala. SSRI exposure and maternal adversity interacted to affect expression of genes such as myelin−associated glycoprotein (Mag) and myelin basic protein (Mbp). We speculate that altered myelination reflects altered brain maturation. In addition, these effects are stronger in males than in females, resembling known behavioral outcomes. Finally, Mag and Mbp expression correlated with DNA methylation, highlighting epigenetic regulation as a potential mechanism for developmental fluoxetine-induced changes in myelination.Competing Interest StatementThe authors have declared no competing interest.