ArticleBrain, behavior, and immunity2023
Early life stress impairs synaptic pruning in the developing hippocampus.
Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07431710 (Utilizing Artificial Intelligence to Optimize Chest Compression Region During Cardio-pulmonary Resuscitation for Patients With Out-of-hospital Cardiac Arrest.), which is not on this map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Utilizing Artificial Intelligence to Optimize Chest Compression Region During Cardio-pulmonary Resuscitation for Patients With Out-of-hospital Cardiac Arrest.
Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
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- The microglial TREM2 receptor programs hippocampal development in a mouse model of childhood deprivation.Brain, behavior, and immunity · 2026Article
- Pediatric traumatic brain injury elicits acute neuroinflammation and long-term changes in social, cognitive, and decision-making behaviors in male and female rats.bioRxiv : the preprint server for biology · 2026Article
- The criticome as the window of becoming: Toward a novel and comprehensive framework for understanding the critical period of information integration in human development.Brain health : lifelong brain resilience and longevity · 2026Article
- Immunity in Rodent Models of Stress.Biological psychiatry · 2026Review
- Germ-free piglets display variable neuroinflammatory-like perturbations in prefrontal cortical microglia.bioRxiv : the preprint server for biology · 2026Article
- Learning, sleep replay and consolidation of contextual fear memories: A neural network model.PLoS computational biology · 2026Article
- Mitophagy-NLRP3 Inflammasome Crosstalk in Parkinson's Disease: Pathogenic Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Cortical similarity networks in the rat brain: Postnatal development and sensitivity to early life stress.Network neuroscience (Cambridge, Mass.) · 2026Article
- Neurobiology of resilience to early life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Microglial MyD88-dependent signaling influences extracellular matrix development and interneuron maturation in the hippocampus.bioRxiv : the preprint server for biology · 2025Article
- Erratic Maternal Care Induces Avoidant-Like Attachment Deficits in a Mouse Model of Early Life Adversity.eNeuro · 2025Article
- The brain cortical similarity network: Development and sensitivity to early life stress in a rat model.bioRxiv : the preprint server for biology · 2025Article
- Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function.Immunity · 2025Article
- Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond.Journal of neuroimmunology · 2025Review
- Hormonal contraceptives in adolescence impact the neuroimmune environment of the medial prefrontal cortex and hippocampus in female rats.Brain, behavior, and immunity · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Early life adversity impairs normal hippocampal function and connectivity in various mammalian species, including humans and rodents. According to the 'cumulative model' the number of early adversities can be summed up to determine the risk for developing psychopathology later in life. In contrast, the 'dimensional model' argues that 'Deprivation' and 'Threat' impact different developmental processes that should not be added in determining clinical outcomes. Here we examine these predictions in male and female mice exposed to a single adversity - limited bedding (LB) - versus mice exposed to multiple adversities - unpredictable postnatal stress (UPS) - focusing on microglia-mediated synaptic pruning in the developing hippocampus. Exposure to both LB and UPS reduced the ramification of microglia, impaired their ability to phagocytose synaptic material in vivo and ex vivo, and decreased expression of TREM2. Abnormal phagocytic activity was associated with increased spine density in CA1 pyramidal neurons that was seen in 17-day-old groups and persisted in peri-pubescent 29-day-old LB and UPS mice. Exposure to LB caused more severe impairment in microglial ramification and synaptic engulfment compared to UPS, outcomes that were accompanied by a UPS-specific increase in the expression of several genes implicated in synaptic pruning. We propose that despite being a single stressor, LB represents a more severe form of early deprivation, and that appropriate levels of hippocampal stimulation during the second and third weeks of life are necessary to support normal microglial ramification and synaptic pruning. Further, impaired synaptic pruning during this critical period of hippocampal development contributes to the abnormal hippocampal function and connectivity seen in UPS and LB later in life.
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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.