Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice View Full Text


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Article Info

DATE

2019-12

AUTHORS

Xiaoliang Xing, Jing Zhang, Kunyang Wu, Beibei Cao, Xianfeng Li, Fang Jiang, Zhengmao Hu, Kun Xia, Jia-Da Li

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. More... »

PAGES

3041

References to SciGraph publications

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  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    9

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-39434-5

    DOI

    http://dx.doi.org/10.1038/s41598-019-39434-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112438958

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30816216


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    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39434-5'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39434-5'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39434-5'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39434-5'


     

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