Project description:In this study we hypothesize that early life stress perturbs the normal function of microglia in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 14-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)
Project description:In this study we hypothesize that early life stress perturbs the normal function of microglial in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 28-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)
Project description:The goal of this project was to identify genes whose expression is modified by age in microglia isolated from the hippocampus of 14 and 28-day old control mice (i.e. normally developing mice). To accomplish this we used two independent cohorts of control mice and identified a list of 76 genes that were significantly regulated by age (p< 0.05) in both cohorts. Data for cohort 1 were extracted from gene expression of P14 and P28 control mice available in the BDS-P14-male series (GSE81036) and BDS-P28-male series (GSE81037). Data for cohort 2 are available in this series. These data are summarized also in Table S3 in Delpech J.C. et al. Early life stress perturbs the maturation of microglial cells in the developing hippocampus, Brain, Behavior and Immunity, 2016 (in preparation).
Project description:The goal of this project was to assess the effects of two paradigms of early life stress on microglial gene expression in the developing hippocampus of 17-day old mice. Sixty thousands microglia were isolated from the hippocampus of 17-day old mice pups exposed to control (CTL), limited bedding (LB) or unpredictable postnatal stress (UPS) conditions and were processed to assess gene expression using the mouse Glia panel (Nanostring, Cat # XT-Mm Glial profiling CSO).
Project description:Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While its role in adult prefrontal cortex (PFC) myelination is known, effects on early-life myelin formation, growth, and integrity remain unclear. Here, we track gene expression in the PFC of germ-free (GF) and non-germ-free (conventional) mice. Alongside metabolomics (HP/LC) from the same region across early life development, in males and females. Metabolomics data available here <URL PLACEHOLDER> In GF mice, we observed sex- and age-dependent alterations in pathways linked to neuronal activity and myelination, with myelin-related transcriptomic changes correlating with functional shifts in neurotransmission- and metabolism-related metabolites over time. Myelin growth and integrity were also affected in a sex- and time-dependent manner. As microglia regulate neuronal activity and engulf myelin, we examined microbiota-microglia interactions and found altered expression of genes involved in microglia maturation and synaptic pruning in both species. In zebrafish larvae, the microbiota influenced the spatial distribution of microglia and oligodendrocytes within the brain and spinal cord. These findings reveal conserved microbiota-mediated modulation of neuronal activity, myelination, and glial maturation in early life, providing a foundation for future studies into these mechanisms. These files contain the RNAseq data underlying this study.
Project description:Sleep supports lifelong brain health and cognition. Sleep loss in early life can drive lasting changes in adult behavior, indicating sleep plays a distinct but poorly understood role supporting brain development. We systematically examined the molecular and behavioral adaptations and synaptic consequences of acute sleep deprivation (SD) in developing and adult mice. Developing mice lack robust adaptations to SD, exacerbating cognitive deficits. Synapse proteome and phosphoproteome analysis revealed profound vulnerability to SD in developing mice, including immediate impacts on synaptogenesis and key aspects of brain development. With maturation, a unified biochemical effect of sleep on synapses emerges, together with robust adaptations and resilience to SD. Our findings show sleep plays a distinct role in early life supporting synapse development, transitioning to homeostatic functions with maturation.
