ArticleBrain, behavior, and immunity2016
Early life stress perturbs the maturation of microglia in the developing hippocampus.
Article in Brain, behavior, and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Meta-analysis of Structural Magnetic Resonance Imaging Studies in Pediatric Posttraumatic Stress Disorder and Comparison With Related Conditions.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Pooled it
- Sevoflurane-induced disruption of critical period Arc signaling drives aberrant microglial synaptic pruning and cognitive deficits.Acta pharmacologica Sinica · 2026Article
- Cytokine-mediated immune-to-brain signaling in neural circuit disorders.Experimental & molecular medicine · 2026Review
- Microglial IL-27 modulates depression-like behaviors induced by postnatal immune activation.Cell reports. Medicine · 2026Article
- A neuroimmune framework for understanding adolescent stress and risk of alcohol misuse.Brain, behavior, & immunity - health · 2026Review
- Disrupted maternal care alters neural-microglia interactions in the primate paralaminar (PL) nucleus of the amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Immunity in Rodent Models of Stress.Biological psychiatry · 2026Review
- Early-life adversity in rodents: Experimental design is of the essence.Neurobiology of stress · 2026Article
- Chronic periodontitis and systemic inflammation in the elderly: implications for neurodegeneration.Journal of neuroinflammation · 2026Review
- Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Early life stress alters microglia in ventral hippocampus and dorsal CA2 associated with anxiety-like behavior in adolescent male rats.Experimental brain research · 2025Article
- CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation.Development (Cambridge, England) · 2025Article
- Neglect and Neurodevelopment: A Narrative Review Understanding the Link Between Child Neglect and Executive Function Deficits.Biomedicines · 2025Review
- From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression.International journal of molecular sciences · 2025Review
- Balancing Microglial Density and Activation in Central Nervous System Development and Disease.Current issues in molecular biology · 2025Review
- Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.Developmental cell · 2025Article
- The link between early-life adversity and later alcohol use disorder: A role for microglia?Neurobiology of stress · 2025Article
- Microglia Morphology in the Developing Primate Amygdala and Effects of Early Life Stress.eNeuro · 2025Article
- Unraveling sex differences in maternal and paternal care impacts on social behaviors and neurobiological responses to early-life adversity.Frontiers in neuroendocrinology · 2025Review
- Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.Journal of neurochemistry · 2025Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Children exposed to abuse or neglect show abnormal hippocampal development and similar findings have been reported in rodent models. Using brief daily separation (BDS), a mouse model of early life stress, we previously showed that exposure to BDS impairs hippocampal function in adulthood and perturbs synaptic maturation, synaptic pruning, axonal growth and myelination in the developing hippocampus. Given that microglia are involved in these developmental processes, we tested whether BDS impairs microglial activity in the hippocampus of 14 (during BDS) and 28-day old mice (one week after BDS). We found that BDS increased the density and altered the morphology of microglia in the hippocampus of 14-day old pups, effects that were no longer present on postnatal day (PND) 28. Despite the normal cell number and morphology seen at PND28, the molecular signature of hippocampal microglia, assessed using the NanoString immune panel, was altered at both ages. We showed that during normal hippocampal development, microglia undergo significant changes between PND14 and PND28, including reduced cell density, decreased ex vivo phagocytic activity, and an increase in the expression of genes involved in inflammation and cell migration. However, microglia harvested from the hippocampus of 28-day old BDS mice showed an increase in phagocytic activity and reduced expression of genes that normally increase across development. Promoter analysis indicated that alteration in the transcriptional activity of PU.1, Creb1, Sp1, and RelA accounted for most of the transcriptional changes seen during normal microglia development and for most of the BDS-induced changes at PND14 and PND28. These findings are the first to demonstrate that early life stress dysregulates microglial function in the developing hippocampus and to identify key transcription factors that are likely to mediate these changes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.