Publication avec DOI
Récupéré
Publication
crossref
Jeremy Veenstra-VanderWeele, Christopher L. Muller, Hideki Iwamoto, Jennifer E. Sauer, W. Anthony Owens, Charisma R. Shah, Jordan Cohen, Padmanabhan Mannangatti, et al.
(2012).
Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.
Proceedings of the National Academy of Sciences, 109(14), 5469-5474.
National Academy of Sciences.
- Date de publication
-
19/03/2012
- Identifiant
-
10.1073/pnas.1112345109
- Auteurs
-
Jeremy Veenstra-VanderWeele,
Christopher L. Muller,
Hideki Iwamoto,
Jennifer E. Sauer,
W. Anthony Owens,
Charisma R. Shah,
Jordan Cohen,
Padmanabhan Mannangatti,
Tammy Jessen,
Brent J. Thompson,
Ran Ye,
Travis M. Kerr,
Ana M. Carneiro,
Jacqueline N. Crawley,
Elaine Sanders-Bush,
Douglas G. McMahon,
Sammanda Ramamoorthy,
Lynette C. Daws,
James S. Sutcliffe,
Randy D. Blakely
- Source
- Proceedings of the National Academy of Sciences
- Détails
- 109(14), 5469-5474
- Type de référence
- article
- Éditeur
- National Academy of Sciences
- Source de métadonnées
- crossref
Résumé
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.
Auteur·ices de l’étude dans cette référence citée