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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Veenstra-vanderweele, Jeremy Ye, Ran Daws, Lynette C. Sanders-bush, Elaine Thompson, Brent J. Sutcliffe, James S. Crawley, Jacqueline N. Owens, W. Anthony Shah, Charisma R. Ramamoorthy, Sammanda Cohen, Jordan Muller, Christopher L. Mannangatti, Padmanabhan Blakely, Randy D. Jessen, Tammy Carneiro, Ana M. Iwamoto, Hideki Mcmahon, Douglas G. Sauer, Jennifer E. Kerr, Travis M. |
| Description | Author Affiliation: Veenstra-VanderWeele J ( Department of Psychiatry, Vanderbilt University, Nashville, TN 37232, USA. j.vvw@vanderbilt.edu); |
| Abstract | Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT(1A) and 5HT(2A) receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Autistic Disorder Genetics Receptors, Serotonin Physiology Serotonin Blood Social Behavior Stereotyped Behavior Animals Physiopathology Disease Models, Animal Homeostasis Mice Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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