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Serotonin : from mouse models to human disorders

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Item Summary

Title: Serotonin : from mouse models to human disorders
Authors: Jensen, Ashley Layne
Keywords: autism
Issue Date: Aug 2014
Publisher: [Honolulu] : [University of Hawaii at Manoa], [August 2014]
Abstract: Autism is an increasingly common neurodevelopmental disorder characterized by deficits in social interactions, impaired communication, and repetitive and stereotyped behaviors. While the etiology of autism is unknown, several lines of evidence implicate dysfunction of the serotonin (5-HT) system in the anatomical and behavioral features of the disorder. Work reported in this series investigated components of the 5-HT system in animal models of autism as well as in post-mortem human brain tissue in an attempt to clarify the role of 5-HT in this disorder. The activity of the central 5-HT system was investigated in the BTBR T+Itpr3tf/J (BTBR) mouse, a strain that displays behaviors consistent with all three diagnostic categories for autism. In comparison to the common C57BL/6J (B6) control strain, BTBR mice showed a pattern of behaviors characterized by reduced frontal orientations in social interactions and altered cortical and cerebellar concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). 5-HT concentrations may be regulated by the serotonin transporter (5-HTT) gene (SLC6A4) and variants in this gene are implicated in autism. Mice with targeted disruptions of SLC6A4 displayed increased stereotyped grooming that is consistent with one of the core symptoms of autism. However, social, aggressive, and communicative behaviors were not altered in SLC6A4 knockout mice. The research reported here also described altered structural and molecular composition in the subventricular zone (SVZ) of individuals with autism. 5-HTT immunoreactivity was significantly increased in the SVZ of autism-diagnosed (AD) individuals when compared to typically-developing controls. Furthermore, structural features of the SVZ in AD cases were suggestive of altered neurogenesis and cellular migration; consistent with the neurodevelopmental nature of this disorder. Collectively, these results provide strong support for the role of serotonergic system dysfunction in the anatomical and behavioral traits characteristic of autism.
Description: Ph.D. University of Hawaii at Manoa 2014.
Includes bibliographical references.
URI/DOI: http://hdl.handle.net/10125/100425
Rights: All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections:Ph.D. - Psychology



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