ArticlePLoS biology2020
Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.Biology of sex differences · 2024Pooled it
- Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.PLoS computational biology · 2026Article
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Transcriptome profile analysis of genes by RNA-sequencing in neonatal maternal separation rats with autistic-like behaviors.Translational pediatrics · 2026Article
- Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches.CNS & neurological disorders drug targets · 2026Review
- Peripheral complement C3 and C4 are associated with clinical features of schizophrenia.Frontiers in psychiatry · 2026Article
- Structural and Functional Analysis of Porcine CR1-like Proteins in C4b-Mediated Immune Responses.Veterinary sciences · 2025Article
- Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.Acta neuropathologica communications · 2025Article
- The Other Side of the Same Coin: Beyond the Coding Region in Amyotrophic Lateral Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.International journal of molecular sciences · 2025Review
- Increased Complement C4 in a Sparse Neuronal Subset Induces Network-Wide Transcriptomic Alterations in the Prefrontal Cortex.bioRxiv : the preprint server for biology · 2025Article
- The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.Molecular psychiatry · 2025Article
- Synaptic Pruning by Microglia: Lessons from Genetic Studies in Mice.Developmental neuroscience · 2025Review
- The role of the microbiota-gut-brain axis in schizophrenia: an immunological perspective.Frontiers in immunology · 2025Review
- Influence of antipsychotic drugs on microglia-mediated neuroinflammation in schizophrenia: perspectives in an astrocyte-microglia co-culture model.Frontiers in psychiatry · 2025Review
- Article
- REVEALS: an open-source multi-camera GUI for rodent behavior acquisition.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease.Science advances · 2024Review
- Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.iScience · 2024Article
- Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is not known whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in schizophrenia patients. We find evidence that microglia-mediated synaptic engulfment is enhanced with increased expression of C4. We also show that C4-dependent circuit dysfunction in the frontal cortex leads to decreased social interactions in juvenile and adult mice. These results demonstrate that increased expression of the schizophrenia-associated gene C4 causes aberrant circuit wiring in the developing prefrontal cortex and leads to deficits in juvenile and adult social behavior, suggesting that altered C4 expression contributes directly to schizophrenia pathogenesis.
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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.