Biology subjects

Maurer, S. V.

Publications and source records attributed to Maurer, S. V..

3 recordsLinked to original sources

bioRxiv2025

Threshold effects of prenatal stress on striatal microglia and relevant behaviors

AbstractPrenatal stress, a risk factor for neurodevelopmental disorders (NDDs), leads to immune alterations, including offspring neuroimmune cells. Differences in offspring outcomes may arise from whether the extent of prenatal stress crosses "thresholds" for effects on specific outcomes. Therefore, we sought to determine offspring outcomes using models with different extents of prenatal stress. We focused on striatal outcomes, because of their relevance for NDDs. Pregnant CD1 mice were assigned to four groups (each: N=6): no stress ("NoS") or one of the following stressors administered three times daily: i.p. saline injections (low prenatal stress, LoS), Interleukin-6 injections as a component of prenatal stress (immune prenatal stress; ImS), or restraint stress + saline injections (high prenatal stress, HiS), embryonic day 12-18. In adult offspring, HiS altered striatal-dependent behavior across males and females, while ImS induced fewer behavioral changes, and LoS did not affect behavior. Adult striatal microglia morphologies were mostly unchanged across groups, with only HiS leading to altered striatal density of minimally ramified cells. However, embryonic striatal microglia were affected by all models of stress, albeit in distinct ways. The HiS model, and to a lesser extent LoS, also influenced immune components of the maternal-fetal interface: placental macrophages. In conclusion, high and immune stress affected adult striatal-dependent behavior, exceeding the threshold necessary for persistent impacts, but all stress models affected embryonic microglia, suggesting that early neuroimmune outcomes had a lower threshold for impacts. Distinct severities and aspects of prenatal stress may therefore underlie different outcomes relevant to NDDs.

neuroscience↗

bioRxiv2024

Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice

Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Maternal diesel exposure and maternal choline supplementation interactions in fetal and placental immune factors

Air pollution causes widespread inflammatory changes in the body and brain. When exposure to air pollution occurs early in development, children exhibit impaired working memory ability (Sunyer et al., 2015). In addition, prenatal exposure to diesel particulate matter (DEP) increases inflammatory cytokine expression in the whole brain of embryonic day 18 (E18) males and leads to adverse long-term negative outcomes (Bolton et al., 2012). In contrast, dietary choline supplementation is negatively correlated with inflammatory cytokine production in adult rats and cultured human cells (Zhang et al., 2018; Jiang et al., 2014). When administered as a supplement to pregnant rats, choline also improves working memory in adulthood (Meck et al., 2008; Meck & Williams, 1999; 1997). The current study sought to determine if prenatal dietary choline supplementation protects against the effects of air pollution in the developing brain and in the placenta and fetal liver. These data revealed region-specific microglial morphology alterations in fetal brain and in inflammatory gene expression in the placenta and fetal liver (specifically, Tnf, Tlr2, Tlr4, and Itgam) due to maternal choline supplementation and/or maternal air pollution exposure. We found that DEP led to changes in microglial morphology in the fetal dentate gyrus of E18 male, but not female, fetuses. In the placenta and fetal liver of males, inflammatory gene expression was affected by both DEP and maternal choline supplementation. However, maternal choline supplementation alone upregulated inflammatory gene expression in females, which may indicate an alteration in maturation rate. These data further contribute to the growing literature indicating region- and tissue-specificity in the developmental immune system in the context of maternal exposures.

neuroscience↗