ArticleMolecular autism2023
Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice.
Article in Molecular autism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 16 citations in OpenAlex.
- Maternal immune activation disrupts epigenomic and functional maturation of cortical excitatory neurons.Molecular psychiatry · 2026Article
- Healing from the Ocean: Targeting Shared Mechanisms in Autism and Epilepsy Using Algae-Derived Compounds.Marine drugs · 2026Review
- Inflammation increases the penetrance of behavioral impairment in Shank3 haploinsufficiency mice - can it explain the behavioral regression in Autism?Molecular psychiatry · 2026Article
- Article
- Generation of the Early-Gestational Maternal Immune Activation Mouse Model to Assess Prenatal Inflammation on Neurodevelopment.Journal of visualized experiments : JoVE · 2026Article
- Inflammation increases the penetrance of behavioral impairment inbioRxiv : the preprint server for biology · 2025Article
- Tau Hypophosphorylation at Ser416 as the Early Molecular Imprint of Maternal Immune Activation: Insights from Female Mice Offspring.International journal of molecular sciences · 2025Article
- Neuroimmune and behavioral changes elicited by maternal immune activation in mice are ameliorated by early postnatal immune stimulation.Brain, behavior, and immunity · 2025Article
- Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons.bioRxiv : the preprint server for biology · 2025Article
- Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.Journal of molecular neuroscience : MN · 2024Article
- Establishment of a two-hit mouse model of environmental factor induced autism spectrum disorder.Heliyon · 2024Article
- Neuroplasticity of children in autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Immune activation state modulates infant engram expression across development.Science advances · 2023Article
- Poly(I:C)-induced maternal immune activation causes elevated self-grooming in male rat offspring: Involvement of abnormal postpartum static nursing in dam.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutism spectrum disorder (ASD) is mainly characterized by deficits in social interaction and communication and repetitive behaviors. Known causes of ASD are mutations of certain risk genes like the postsynaptic protein SHANK3 and environmental factors including prenatal infections.
methodsTo analyze the gene-environment interplay in ASD, we combined the Shank3Δ11-/- ASD mouse model with maternal immune activation (MIA) via an intraperitoneal injection of polyinosinic/polycytidylic acid (Poly I:C) on gestational day 12.5. The offspring of the injected dams was further analyzed for autistic-like behaviors and comorbidities followed by biochemical experiments with a focus on synaptic analysis.
resultsWe show that the two-hit mice exhibit excessive grooming and deficits in social behavior more prominently than the Shank3Δ11-/- mice. Interestingly, these behavioral changes were accompanied by an unexpected upregulation of postsynaptic density (PSD) proteins at excitatory synapses in striatum, hippocampus and prefrontal cortex. LIMITATIONS: We found several PSD proteins to be increased in the two-hit mice; however, we can only speculate about possible pathways behind the worsening of the autistic phenotype in those mice.
conclusionsWith this study, we demonstrate that there is an interplay between genetic susceptibility and environmental factors defining the severity of ASD symptoms. Moreover, we show that a general misbalance of PSD proteins at excitatory synapses is linked to ASD symptoms, making this two-hit model a promising tool for the investigation of the complex pathophysiology of neurodevelopmental disorders.
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