Department of Psychiatry
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Molecular Biology | Nervous System Diseases | Neuroscience and Neurobiology | Psychiatry | Psychiatry and Psychology
Autism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit gene GABRA4 are reported in patients with ASD, we eliminated the Gabra4 gene in mice and found that the Gabra4 knockout mice showed autistic-like behavior, enhanced spatial memory, and attenuated susceptibility to pentylenetetrazol-induced seizures, a constellation of symptoms resembling human high-functioning autism. To search for potential molecular pathways involved in these phenotypes, we performed a hippocampal transcriptome profiling, constructed a hippocampal interactome network, and revealed an upregulation of the NMDAR system at the center of the converged pathways underlying high-functioning autism-like and anti-epilepsy phenotypes.
Autism, Epilepsy, Gabra4, Interactome, NMDARs, Transcriptome
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© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
Fan C, Gao Y, Liang G, Huang L, Wang J, Yang X, Shi Y, Dräger UC, Zhong M, Gao TM, Yang X. Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy. Mol Autism. 2020 Feb 7;11(1):13. doi: 10.1186/s13229-020-0318-9. PMID: 32033586; PMCID: PMC7007694. Link to article on publisher's site
Fan C, Gao Y, Liang G, Huang L, Wang J, Yang X, Shi Y, Drager UC, Zhong M, Gao T, Yang X. (2020). Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy. Open Access Publications by UMMS Authors. https://doi.org/10.1186/s13229-020-0318-9. Retrieved from https://escholarship.umassmed.edu/oapubs/4164
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