ArticleTranslational psychiatry2021
Cntn4, a risk gene for neuropsychiatric disorders, modulates hippocampal synaptic plasticity and behavior.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Shared and Sex-Specific Genetic Risk for Parkinson's Disease Risk Across European Populations.medRxiv : the preprint server for health sciences · 2026Article
- Role of CNTN6 in neurodevelopment and neuropathology.Frontiers in neuroscience · 2026Review
- Cntn4 Gene Deficiency Promotes Autism-Like Phenotypes Associated with Gut Microbiota Perturbations and Gut-Brain Axis Metabolomic Alterations in Mice.Molecular neurobiology · 2025Article
- Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in AppAging cell · 2025Article
- Genome-wide association study of childhood B-cell acute lymphoblastic leukemia reveals novel African ancestry-specific susceptibility loci.Nature communications · 2025Article
- Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.npj metabolic health and disease · 2025Article
- MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types.Nature neuroscience · 2025Article
- Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications.Neurobiology of stress · 2025Article
- STsisal: a reference-free deconvolution pipeline for spatial transcriptomics data.Frontiers in genetics · 2025Article
- Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1.Cancer research · 2024Article
- Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission.IBRO neuroscience reports · 2024Article
- CNTN4 modulates neural elongation through interplay with APP.Open biology · 2024Article
- iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.International journal of molecular sciences · 2024Article
- Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders.Journal of neurodevelopmental disorders · 2023Article
- Association between suicidal ideation and tandem repeats inFrontiers in psychiatry · 2023Article
- Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter?Diagnostics (Basel, Switzerland) · 2022Article
- Contribution of copy number variations to the risk of severe eating disorders.Psychiatry and clinical neurosciences · 2022Article
- Deep learning predicts DNA methylation regulatory variants in the human brain and elucidates the genetics of psychiatric disorders.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas.Nature ecology & evolution · 2022Article
- Gene editing in monogenic autism spectrum disorder: animal models and gene therapies.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodevelopmental and neuropsychiatric disorders, such as autism spectrum disorders (ASD), anorexia nervosa (AN), Alzheimer's disease (AD), and schizophrenia (SZ), are heterogeneous brain disorders with unknown etiology. Genome wide studies have revealed a wide variety of risk genes for these disorders, indicating a biological link between genetic signaling pathways and brain pathology. A unique risk gene is Contactin 4 (Cntn4), an Ig cell adhesion molecule (IgCAM) gene, which has been associated with several neuropsychiatric disorders including ASD, AN, AD, and SZ. Here, we investigated the Cntn4 gene knockout (KO) mouse model to determine whether memory dysfunction and altered brain plasticity, common neuropsychiatric symptoms, are affected by Cntn4 genetic disruption. For that purpose, we tested if Cntn4 genetic disruption affects CA1 synaptic transmission and the ability to induce LTP in hippocampal slices. Stimulation in CA1 striatum radiatum significantly decreased synaptic potentiation in slices of Cntn4 KO mice. Neuroanatomical analyses showed abnormal dendritic arborization and spines of hippocampal CA1 neurons. Short- and long-term recognition memory, spatial memory, and fear conditioning responses were also assessed. These behavioral studies showed increased contextual fear conditioning in heterozygous and homozygous KO mice, quantified by a gene-dose dependent increase in freezing response. In comparison to wild-type mice, Cntn4-deficient animals froze significantly longer and groomed more, indicative of increased stress responsiveness under these test conditions. Our electrophysiological, neuro-anatomical, and behavioral results in Cntn4 KO mice suggest that Cntn4 has important functions related to fear memory possibly in association with the neuronal morphological and synaptic plasticity changes in hippocampus CA1 neurons.
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