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Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder
Thesis (MSc)--Stellenbosch University, 2025.
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Stellenbosch : Stellenbosch University
2026
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| _version_ | 1867613901190856704 |
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| access_status_str | Open Access |
| author | Moodley, Tamera |
| author2 | Smith, Carine |
| author_browse | Moodley, Tamera Smith, Carine |
| author_facet | Smith, Carine Moodley, Tamera |
| author_sort | Moodley, Tamera |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/134713 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:43:30.254Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/134713 Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder Moodley, Tamera Smith, Carine Pretorius, Lesha Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology. Autism spectrum disorders Proteomics Amines -- Metabolism -- Disorders Thesis (MSc)--Stellenbosch University, 2025. Moodley, T. 2025. Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder. Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/6206c7b9-7ef4-4fd0-9bf8-7983a3a4106f ENGLISH ABSTRACT: Background & Aim Autism spectrum disorder (ASD) is characterised by impairments in three principal areas: reciprocal social interaction, communication, and repetitive or restricted behaviours. Dysregulation of monoamine signalling has been implicated in ASD, while trace amines are emerging as modulators of monoaminergic neurotransmission, though their roles remain poorly defined. In addition, clinical and preclinical studies highlight sex differences in ASD prevalence and behavioural expression, underscoring the need for models that account for biological sex. This study aimed to investigate sex-specificity of behavioural and proteomic dysregulation in an established and widely used adult zebrafish model of ASD. Methods Successful induction of a zebrafish valproic acid (VPA) model of ASD was confirmed through assessment of known core hallmarks of the VPA model, at the larval stage through behavioural assessment (light–dark transition test) and immunostaining. Retention of the phenotype, as well as presence of anxiety was assessed at the adult stage using behavioural assays including the novel tank test, social preference test, and mirror biting test, as well as neurochemical profiling of serotonergic, dopaminergic and trace aminergic signalling via proteomic assessment. Results Larval zebrafish exposed to VPA displayed reduced basal activity, exaggerated startle responses, and prolonged freezing in the light–dark transition test, confirming the induction of an ASD-like phenotype. In adulthood, VPA-exposed fish exhibited persistent behavioural abnormalities, including anxiety-like behaviour in the novel tank test, social avoidance in the social preference test, and altered aggression in the mirror biting test. Sex-specific effects were evident, with females showing more pronounced anxiety-like responses, subtle increases in social engagement, and delayed aggressive behaviours, suggesting compensatory coping strategies. At the molecular level, VPA exposure was associated with decreased serotonin levels and altered histamine receptor H1 expression in larvae, while in adults, significant downregulation of tyrosine hydroxylase and tryptophan hydroxylase 2 was observed in the VPA group. Additionally, females showed reduced serotonin transporter and tyrosine hydroxylase expression compared to males, implicating sex-dependent modulation of monoaminergic systems in the observed behavioural phenotypes. Conclusion Using the VPA exposure model of ASD, we reveal mechanistic links between monoaminergic and trace aminergic dysregulation and ASD-like phenotypes, and underscores the importance of incorporating sex as a biological variable. Future studies should employ targeted metabolomic approaches to identify the contribution of trace amines and inform development of sex-specific therapeutic interventions. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Masters 2026-01-05T07:55:29Z 2026-01-05T07:55:29Z 2025-12 Thesis https://scholar.sun.ac.za/handle/10019.1/134713 Stellenbosch University viii, 66 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Autism spectrum disorders Proteomics Amines -- Metabolism -- Disorders Moodley, Tamera Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title | Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title_full | Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title_fullStr | Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title_full_unstemmed | Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title_short | Proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| title_sort | proteomic assessment of trace amine metabolism dysregulation in autism spectrum disorder |
| topic | Autism spectrum disorders Proteomics Amines -- Metabolism -- Disorders |
| url | https://scholar.sun.ac.za/handle/10019.1/134713 |
| work_keys_str_mv | AT moodleytamera proteomicassessmentoftraceaminemetabolismdysregulationinautismspectrumdisorder |