dc.contributor.author | Li, Zhu | |
dc.contributor.author | Jagadapillai, Rekha | |
dc.contributor.author | Gozal, Evelyne | |
dc.contributor.author | Barnes, Gregory | |
dc.date.accessioned | 2020-06-04T16:37:19Z | |
dc.date.available | 2020-06-04T16:37:19Z | |
dc.date.issued | 2019-08 | |
dc.identifier.citation | Li, Z., Jagadapillai, R., Gozal, E., & Barnes, G. (2019). Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades. Molecular neurobiology, 56(8), 5520–5538. https://doi.org/10.1007/s12035-018-1450-9 | en_US |
dc.identifier.issn | 0893-7648 | |
dc.identifier.uri | http://hdl.handle.net/1803/10036 | |
dc.description.abstract | Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the genetic basis of the comorbid occurrence of autism and epilepsy is unknown. The aberrant development of GABAergic circuitry is a possible risk factor in autism and epilepsy. Molecular biological approaches were used to test the hypothesis that cell-specific genetic variation in mouse homologs affects the formation and function of GABAergic circuitry. The empirical analysis with mice homozygous null for one of these genes, Sema 3F, in GABAergic neurons substantiated these predictions. Notably, deletion of Sema 3F in interneurons but not excitatory neurons during early development decreased the number of interneurons/neurites and mRNAs for cell-specific GABAergic markers and increased epileptogenesis and autistic behaviors. Studies of interneuron cell-specific knockout of Sema 3F signaling suggest that deficient Sema 3F signaling may lead to neuroinflammation and oxidative stress. Further studies of mouse KO models of ASD genes such as Sema 3F or NRP2 may be informative to clinical phenotypes contributing to the pathogenesis in autism and epilepsy patients. | en_US |
dc.description.sponsorship | This work was supported in part by a Partnership for Pediatric Epilepsy Research grant, Autism Speaks, a grant from the Vanderbilt Molecular Toxicology Center, and a Norton Children's Hospital grant (all for G.N.B). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Molecular Neurobiology | en_US |
dc.rights | 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. | |
dc.source.uri | https://pubmed.ncbi.nlm.nih.gov/30635860/ | |
dc.subject | Autism | en_US |
dc.subject | Epilepsy | en_US |
dc.subject | Semaphorin | en_US |
dc.subject | Interneuron | en_US |
dc.subject | Hippocampus | en_US |
dc.subject | Development | en_US |
dc.title | Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1007/s12035-018-1450-9 | |