The Effect of the Herbicide Glyphosate on Neurodevelopment and its Influences on Two Genetic Zebrafish Models of Autism
Date
2024-12-27
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Abstract
Glyphosate is the world’s most sprayed herbicide, leading to near ubiquity in the environment and increasing exposure for humans and wildlife. Initially glyphosate was thought to be safe for animals since it targets a molecular pathway found only in plants and bacteria, which facilitated the rapid adoption of glyphosate into mainstream agricultural practices. However, growing evidence suggests that glyphosate might be toxic across a wide range of organisms, including humans, leading to growing concerns of glyphosate’s effects on human health. Epidemiolocal findings show a strong correlation between increasing human glyphosate exposure and the rising rates of Autism Spectrum Disorder (ASD) diagnoses, raising the intriguing notion that glyphosate is somehow contributing to the etiology of ASD. The gene x environment hypothesis of ASD suggests that environmental factors, such as herbicides, may interact with autism alleles to perturb neurodevelopment to cause autism. Within this thesis, first I use zebrafish as a model system to characterize the behavioural (Chapter 3) and molecular/cellular (Chapter 4) effects of embryonic exposure to the active ingredient glyphosate alone as well as its commercial formulation RoundUp that also contains a mixture of surfactants that might be toxic. I show that embryonic exposure (10 hours-post fertilization (hpf)-48 hpf) to glyphosate singly or commercial RoundUp causes a range of behavioural deficits, with RoundUp exposed zebrafish showing a stronger phenotype. I also demonstrate that embryonic exposure to RoundUp disrupts neurogenesis and axonogenesis, and causes a concomitant increase in neuronal activity by 5 days-post fertilization (dpf). Next, I use two genetic zebrafish models whereby ASD genes have been mutated. I characterize these ASD lines and test a potential gene x environment interaction by assaying the effects of glyphosate in these zebrafish ASD models (Chapter 5). I show that ASD zebrafish have defects in morphology, behaviour, and brain activity. Behavioural and brain activity phenotypes are modulated with Roundup exposure in a genotype-dependant manner. Combined, these studies demonstrate that glyphosate and its commercial formulation RoundUp is toxic to developing brains in vivo and provide some evidence that exposure to glyphosate-based herbicides might contribute to the increasing rise of ASD diagnoses in children.
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Keywords
zebrafish, glyphosate, Roundup, neurodevelopment
Citation
Lacroix, R. (2025). The effect of the herbicide glyphosate on neurodevelopment and its influences on two genetic zebrafish models of autism (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.