ArticleMolecular psychiatry2021
Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Biallelic loss-of-function variants in DSCAM cause a neurodevelopmental syndrome with nystagmus and retinal dysfunction.HGG advances · 2026Article
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Future Directions for Studying the Potential of Mammalian Dscam in Autism Spectrum Disorder and Alzheimer's Disease: Insights from Dose Sensitivity.Molecular neurobiology · 2025Review
- Neurometabolic profiles of autism spectrum disorder patients with genetic variants in specific neurotransmission and synaptic genes.Scientific reports · 2025Article
- Clinical Application of a Customized Gene Panel for Identifying Autism Spectrum Disorder-Associated Variants.Medicina (Kaunas, Lithuania) · 2025Article
- Deficiency of FABP7 Triggers Premature Neural Differentiation in Idiopathic Normocephalic Autism Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring perspectives of Dscam for cognitive deficits: a review of multifunction for regulating neural wiring in homeostasis.Frontiers in molecular neuroscience · 2025Review
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Mutation in the mitochondrial chaperone TRAP1 leads to autism with more severe symptoms in males.EMBO molecular medicine · 2024Article
- Cognitive behavioral phenotyping of DSCAM heterozygosity as a model for autism spectrum disorder.Genes, brain, and behavior · 2024Article
- Central Causation of Autism/ASDs via Excessive [CaBrain sciences · 2024Review
- Review
- Synaptic ensembles between raphe and DScience advances · 2022Article
- Brain physiome: A concept bridgingBioactive materials · 2022Review
- Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells.Translational psychiatry · 2022Review
- The GluN2B-Trp373 NMDA Receptor Variant is Associated with Autism-, Epilepsy-Related Phenotypes and Reduces NMDA Receptor Currents in Rats.Neurochemical research · 2022Article
- Alterations of presynaptic proteins in autism spectrum disorder.Frontiers in molecular neuroscience · 2022Review
- Cell culture research in aging and Alzheimer's disease: The strategic use/reuse of untreated controls and savings people's tax dollars.Journal of Alzheimer's disease reportsReview
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.
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