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The development of animal models for autism: A gene-environment approach

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thesis
posted on 2021-11-15, 21:14 authored by Ranger, Peter

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterised by social, communicative, and behavioural deficits. Despite decades of research in this field, effective pharmacological treatments for ASD are still lacking and better animal models for this disorder are urgently needed. Although it is now well understood that both genetic and environmental influences play a role in the aetiology of ASD, most existing animal models for this disorder only take into account one of these aetiological contributors and have largely ignored investigating an interaction. The main aim of this thesis was to develop a novel animal model for ASD that demonstrated higher construct validity than traditional models by using a gene-environment approach. To this aim, two previously established environmental risk factor-based models for ASD were each combined with a genetic rat model that mimicked a genotype associated with ASD. Specifically, a maternal immune activation model (modelled via prenatal administration of lipopolysaccharide) and a prenatal exposure to valproate model (modelled via prenatal administration of valproate) were both combined with a serotonin transporter (SERT) knockout rat model. Next, experimental rats were investigated in a variety of paradigms designed to detect behavioural, biochemical, and immunological outcomes related to ASD. This thesis tested the hypothesis that rats with a genetically compromised SERT function would be more vulnerable to the impacts of the two environmental risk factors. Collectively, the data from this thesis show that rats with a genetically compromised SERT function are not more vulnerable to the impacts of a maternal immune activation or prenatal exposure to VPA. In fact, at least with regards to prenatal exposure to valproate, rats with a compromised SERT function actually appeared more resilient to ASD-like outcomes.

History

Copyright Date

2016-01-01

Date of Award

2016-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Neuroscience

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Doctoral

Degree Name

Doctor of Philosophy

ANZSRC Type Of Activity code

970117 Expanding Knowledge in Psychology and the Cognitive sciences

Victoria University of Wellington Item Type

Awarded Doctoral Thesis

Language

en_NZ

Victoria University of Wellington School

School of Psychology

Advisors

Ellenbroek, Bart; Harper, Dave