Biology subjects

Richetto, J.

Publications and source records attributed to Richetto, J..

3 recordsLinked to original sources

bioRxiv2026

Preconceptional social isolation alters inflammatory and transcriptional signalling across the placenta-fetal brain axis

Maternal depression and psychosocial adversity during pregnancy are associated with altered offspring neurodevelopment, yet the molecular processes linking maternal state to the developing fetus remain incompletely understood. The placenta is positioned to sense and respond to maternal physiological signals, but how placental molecular responses relate to those in the developing brain is unclear. Here, we used a mouse model of prolonged social isolation initiated before conception and maintained throughout pregnancy to investigate inflammatory and transcriptional alterations across matched placenta and fetal-brain samples at gestational day 18. Maternal social isolation altered cytokine profiles in both tissues and induced extensive transcriptional changes in the placenta, with a more restricted response in the fetal brain. Functional analyses identified alterations in placental immune, metabolic and transport-related programmes and fetal-brain immune, neuronal and proliferative processes. Although sex-stratified analyses revealed different transcriptional profiles in male and female tissues, formal maternal housing x fetal-sex interaction testing did not identify significant gene-level interaction effects. Cross-tissue co-expression analysis initially identified extensive covariation between social-isolation-responsive placental and fetal-brain modules; however, most associations were attenuated after accounting for their shared relationship with maternal housing. An exposure-independent network analysis nevertheless identified an inverse pregnancy-level association between a placental module enriched for immune and interferon-related signalling and a fetal-brain module enriched for cell-cycle and proliferative processes. Together, these findings show that prolonged maternal social adversity is associated with coordinated but tissue-distinct molecular alterations across the placenta-fetal brain axis and demonstrate the importance of distinguishing parallel responses to a common maternal environment from direct cross-tissue molecular coupling.

neuroscience↗

bioRxiv2023

Microglia undergo transcriptional, translational and functional adaptations to dark and light phases in laboratory mice

Microglia cells are increasingly recognized to contribute to brain health and disease. Preclinical studies using laboratory rodents are essential to advance our understanding of the physiological and pathophysiological functions of these cells in the central nervous system. Rodents are nocturnal animals, and they are mostly maintained in a defined light-dark cycle within animal facilities, with many laboratories investigating microglial molecular and functional profiles during the animals light (sleep) phase. However, only a few studies have considered possible differences in microglial functions between the active and sleep phases. Based on initial evidence suggesting that microglial intrinsic clock genes can affect their phenotype, we sought to investigate differences in transcriptional, proteotype and functional profiles of microglia between light (sleep) and dark (active) phases, and how these changes are affected in pathological models. We found marked transcriptional and proteotype differences between microglia harvested during the light or dark phase. Amongst others, these differences related to genes and proteins associated with immune responses, motility, and phagocytosis, which were reflected by functional alterations in microglial synaptic pruning and response to bacterial stimuli. Possibly accounting for such circadian changes, we found RNA and protein regulation in SWI/SNF and NuRD chromatin remodeling complexes between light and dark phases. Importantly, we show that microglial circadian transcriptional changes are impaired in a model of immune-mediated neurodevelopmental disorders. Our findings emphasize the importance of considering circadian factors in studying microglial cells and indicate that implementing a circadian perspective is pivotal for advancing our understanding of their physiological and pathophysiological roles in brain health and disease. This may also open novel avenues towards therapeutic strategies for modulating microglial functions during specific windows of the active or sleep phase.

neuroscience↗

bioRxiv2020

Enzymatic dissociation induces transcriptional and proteotype bias in brain cell populations

Different cell isolation techniques exist for transcriptomic and proteotype profiling of brain cells. Here, we provide a systematic investigation of the influence of different cell isolation protocols on transcriptional and proteotype profiles in mouse brain tissue by taking into account single-cell transcriptomics of brain cells, proteotypes of microglia and astrocytes, and flow cytometric analysis of microglia. We show that standard enzymatic digestion of brain tissue at 37{degrees}C induces profound and consistent alterations in the transcriptome and proteotype of neuronal and glial cells, as compared to an optimized mechanical dissociation protocol at 4{degrees}C. These findings emphasize the risk of introducing technical biases and biological artefacts when implementing enzymatic digestion-based isolation methods for brain cell analyses.

neuroscience↗