ArticleImmunity2021
Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 129 citations in OpenAlex.
- Associations between chronic placental inflammation, fetal brain development and later autism traits.Brain, behavior, & immunity - health · 2026Article
- Prenatal Stress Induced by Maternal Immune Activation Disrupts GABAergic Inhibition and Mossy Fiber Plasticity in the Rat Dentate Gyrus-CA3 Circuit.Hippocampus · 2026Article
- Decoding neurodevelopment risks of exposures to intoxication, infection, and trauma during pregnancy.Pregnancy (Hoboken, N.J.) · 2026Review
- Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- The Impact of Childhood Trauma on Neuropsychological Disorders and Its Intergenerational Transmission Mechanisms.Behavioral sciences (Basel, Switzerland) · 2026Review
- Targeting microglial circMBNL1 unlocks a novel nanomedicine therapeutic strategy for major depressive disorder.Journal of nanobiotechnology · 2026Article
- Exploring offspring behaviour after prenatal COVID-19 vaccination in mice.Translational psychiatry · 2026Article
- Autism subtypes identified using cross-species functional connectivity analyses.Nature neuroscience · 2026Article
- Prenatal training grounds: the developmental origins of chronic immune disease.Journal of translational medicine · 2026Review
- Neurodevelopmental comorbidities in juvenile systemic autoimmune and autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Prenatal and postnatal effects of gestational immune activation on synaptic and neurodevelopmental pathways via epigenetic mechanisms.Translational psychiatry · 2026Article
- Microglial Maturation and Functional Heterogeneity: Mechanistic Links to Neurodevelopmental Disorders.International journal of molecular sciences · 2026Review
- Vagus nerve stimulation as an anti-inflammatory therapy for maternal immune activation-induced alterations in offspring microglia and neurodevelopment.Frontiers in neuroscience · 2026Review
- Neuroinflammation and white matter microstructure as mediators of cognitive deficits in offspring of parents with bipolar disorder.Brain communications · 2026Article
- FMRP regulation of STAT3-MYC signaling is critical for adult hippocampal neurogenesis and cognitive flexibility.Cell death and differentiation · 2026Article
- The Role of Cytokines in the Development and Functioning of the Hypothalamic-Pituitary-Gonadal Axis in Mammals in Normal and Pathological Conditions.International journal of molecular sciences · 2025Review
- Decreased hippocampal neurite density in late-middle-aged adults following prenatal exposure to higher levels of maternal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maternal stressors disrupt mouse placental proteome and fetal brain development in a sex-specific fashion through inflammation and oxidative stress.Molecular psychiatry · 2025Article
- IL-6 Inhibition Partially Ameliorates Maternal Immune Activation-Induced Autism-Like Behavioral Abnormalities in Mice.Current issues in molecular biology · 2025Article
- Prenatal Inflammation Reprograms Hypothalamic-Pituitary-Gonadal Axis Development in Female Rats.Inflammation · 2025Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.
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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 Socratic graph.