Biology subjects

Ramsteijn, A. S.

Publications and source records attributed to Ramsteijn, A. S..

3 recordsLinked to original sources

bioRxiv2020

Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

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.

neuroscience↗

bioRxiv2019

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

In the Western world, 2-5% of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) -0.28 [-0.38, -0.18]), more passive stress coping (SMD -0.37 [-0.52, -0.23]), and less efficient sensory processing (SMD -0.37 [-0.69, -0.06]) in SSRI-versus vehicle-exposed animals. No differences were found for anxiety (p=0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects. HighlightsO_LIPerinatal SSRI exposure in rodents alters outcomes in three behavioral domains. C_LIO_LIIt leads to reduced activity, passive stress coping, and weaker sensory processing. C_LIO_LIFemales are understudied but seem to be less vulnerable than males. C_LIO_LIEarly postnatal exposure in rodents leads to the largest effects on behavior. C_LIO_LIThis is equivalent to the third trimester of pregnancy in humans. C_LI

animal behavior and cognition↗

bioRxiv2018

Antidepressant treatment modulates the gut microbiome and metabolome during pregnancy and lactation in rats with a depressive-like phenotype

BackgroundUp to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during and after pregnancy to manage mood disorders, with possible implications for the developing offspring. The microbiota within the gastrointestinal tract contributes to the regulation of serotonin synthesis. However, the interaction between maternal depression, SSRI use, bacterial community composition, and availability of microbiota-derived metabolites during pregnancy and lactation is not clear and may be consequential to the long-term health of mother and offspring. To determine the impact of SSRI treatment on maternal microbial community dynamics, we conducted these studies in a rat model of maternal vulnerability (MV). All MV females are on a background of genetic vulnerability, where rats exposed to early life stress (sMV) develop a depressive-like phenotype. In adulthood, sMV- and control (cMV) females were treated with either the SSRI fluoxetine (FLX) or the vehicle (Veh) throughout pregnancy and lactation. High-resolution 16S ribosomal RNA gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively.\n\nResultsThe diversity, structure, and composition of the fecal bacterial community differed between pregnancy and lactation. Shifts in microbiota composition were accompanied by changes in fecal metabolite availability. FLX altered some key features of the transition from pregnancy to lactation, but only in females exposed to early life stress (sMV-Veh vs sMV-FLX). For instance, sMV-FLX females had lower fecal availability of the amino acids serine, proline, and aspartic acid than sMV-Veh females. These metabolite concentrations correlated negatively with the relative abundance of bacterial taxa Prevotella, Ruminococcus, and Oscillospira.\n\nConclusionsOur studies demonstrate an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in sMV rats, possibly through parallel changes in the maternal gut microbiome. Since maternal microbial metabolites contribute to health outcomes in offspring, insults to the maternal microbiome by SSRIs might have inter-generational consequences.

microbiology↗