ArticleScientific reports2019
Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- Genetic mutations and synaptic dysfunctions in social interaction disorders: insights from invertebrate models to humans.Metabolic brain disease · 2026Review
- Lower Striatal and Cortical Calretinin Interneuron Density Associated With Altered Social Behavior in Cntnap2 Knockout Mice.Autism research : official journal of the International Society for Autism Research · 2026Article
- Nitric Oxide-Mediated S-Nitrosylation of TSC2 Drives mTOR dysregulation across Shank3 and Cntnap2 Models of Autism Spectrum Disorder.Molecular psychiatry · 2026Article
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Targeting the mTOR Pathway with Natural Products: A Potential Therapeutic Approach for Autism Spectrum Disorders.Current neuropharmacology · 2026Review
- Unveiling the multitarget mechanism of Liuwei Dihuang decoction in autism spectrum disorder via network pharmacology and molecular docking.Scientific reports · 2025Article
- Article
- Review
- The Possible Role of Postnatal Biphasic Dysregulation of IGF-1 Tone in the Etiology of Idiopathic Autism Spectrum Disorder.International journal of molecular sciences · 2025Review
- Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.PLoS biology · 2025Article
- GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2Biological psychiatry global open science · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Article
- RPS23RG1 inhibits SORT1-mediated lysosomal degradation of MDGA2 to protect against autism.Theranostics · 2025Article
- The Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.Cells · 2024Review
- Transient CSF1R inhibition ameliorates behavioral deficits in Cntnap2 knockout and valproic acid-exposed mouse models of autism.Journal of neuroinflammation · 2024Article
- nlr-1/CNTNAP regulates dopamine circuit structure and foraging behaviors in C. elegans.Communications biology · 2024Article
- Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Exploring key genes and pathways associated with sex differences in autism spectrum disorder: integrated bioinformatic analysis.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autism spectrum disorders (ASD) form a heterogeneous, neurodevelopmental syndrome characterized by deficits in social interactions and repetitive behavior/restricted interests. Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models. However, it is still unknown if dysregulation of mTOR signaling is responsible for the ASD-related deficit caused by other genes mutations. Contactin associated protein-like 2 (CNTNAP2) is the first widely replicated autism-predisposition gene. Mice deficient in Cntnap2 (Cntnap2-/- mice) show core ASD-like phenotypes, and have been demonstrated as a validated model for ASD-relevant drug discovery. In this study, we found hyperactive Akt-mTOR signaling in the hippocampus of Cntnap2-/- mice with RNA sequencing followed with biochemical analysis. Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2-/- mice. We further showed that the effect of LY294002 and rapamycin on social behaviors is reversible. Our results thus identified hyperactive Akt-mTOR signaling pathway as a therapeutic target for abnormal social behavior in patients with dysfunction of CNTNAP2.
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