Exploring Neuroanatomical and Molecular Distinctions in a Maternal Hypothyroid Mouse Model of Autism Spectrum Disorder

Tynan, Ronan (2024) Exploring Neuroanatomical and Molecular Distinctions in a Maternal Hypothyroid Mouse Model of Autism Spectrum Disorder. Doctoral thesis, University of East Anglia.

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Abstract

This thesis delves into the potential neuroanatomical and molecular characteristics of a maternal hypothyroid model of autism spectrum disorder (ASD) and compares them to those of control mice. We utilise advanced imaging techniques, such as X-absorption micro computed tomography (μCT) scanning and immunohistochemistry (IHC) analysis. Our focus is on examining the effects of maternal hypothyroidism, which is induced by a pharmacological treatment involving 0.1% Methimazole (MMI) in drinking water, administered from the start of gestation (E0) until the 13.5th day of embryonic development (E13.5). Notably, the offspring of MMI-treated mothers exhibit behavioural characteristics associated with autism during neurodevelopment in a sexually dimorphic manner.

Chapter 2 focuses on the use of Micro-computed tomography (μCT) to assess large white matter structures such as the corpus callosum (CC) and fornix, and examines the deep cerebellar nuclei (DCN). However, the findings were inconclusive, with no observable difference between control and MMI-treated mice, highlighting the complex relationship between maternal thyroid function and ASD.

Chapter 3 delves into the molecular landscape of prenatal (E16.5) transient hypothyroid mouse brains. We detected significant changes in T-box, brain, 1 (TBR1) staining of the fastigial nucleus, and RAR-related orphan receptor alpha (RoRα) staining of Purkinje cells. These findings suggest a role for early rhombic lip lineage formation in the role of thyroid hormones (THs) in ASD.

Chapter 4 extends the molecular investigations of juveniles. P30 transient hypothyroid mouse brains. Contrary to expectations, no significant enduring molecular changes were observed, suggesting a differing underlying reason for the observed behavioural changes in the model. These results demonstrate the complex links between maternal thyroid status and early cerebellar development that may lead to neurodevelopmental disorders such as ASD. This study enhances our understanding of the network of genes potentially involved in ASD and TH disruption, indicating a possible link between THs, ASD-associated gene expression, and neurodevelopment.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	07 Apr 2025 14:45
Last Modified:	07 Apr 2025 14:45
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98980
DOI:

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