The external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore... Show moreThe external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore encounter microbiota at the exposure interface. Many antimicrobial substances have been found to disturb beneficial interactions between microbiota and the host, thereby impairing host health. Nanomaterials exhibit nanoscale properties that could affect host health in two additional, understudied, microbiota-dependent ways. Firstly, owing to their large surface area, adsorption interactions between nanomaterials, microbial metabolites and microbes could alter the identity and colloidal stability of nanomaterials, and may influence the dispersal of microbes. Secondly, the immuno-modulatory effects of microbiota could affect the sensitivity of hosts to immunotoxic nanomaterials. In this dissertation, we use a combination of computational techniques and zebrafish larvae experiments to unravel and quantify these interactions. We predict the affinity of microbial metabolites to carbon and metal nanomaterials, and show that titanium dioxide nanoparticles can affect the dispersal of microbes through aquatic ecosystems, and across different life stages of oviparous animals. Additionally, we provide insight into microbiota-dependent signaling pathways that affect the sensitivity of zebrafish larvae to particle-specific, immunotoxic effects of silver nanoparticles. Altogether, these results contribute to mechanistic pathways for microbiota-inclusive nanomaterial safety assessment. Show less
In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the... Show moreIn this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the role of the ECS in regulating locomotion and anxiety, and its interaction with the hypothalamic-pituitary-interrenal (HPI) axis, or stress axis. This study has provided us with an interesting animal model which allows for pharmacological screening of Cnr1 agonists, and their involvement in the CNS, as shown by a change in locomotion, anxiety-like behavior and HPI axis activity. The zebrafish larval model can be used as a complementary model to the existing rodent animal models, to study the ECS. The zebrafish larval model brings several interesting features, such as optical transparency and possibilities for high-throughput screening. Furthermore, a complete ECS is present, there is lack of endogenous activity, allowing for exogenous compound screening, and zebrafish data is generally in line with rodent literature. Since the ECS is involved in many diseases, more research of this system may result in the discovery of novel drugs and drug targets. Show less
The main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological... Show moreThe main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological modulation with drugs. Several behavioural parameters of larval zebrafish were used to evaluate anxiety-like behaviours, which are locomotion, startle response, and thigmotaxis. In addition to this, behavioural assays are also used to screen synthetic anxiolytics commonly used in the treatment of anxiety disorders. Finally, the toxic effects of the synthetic and herbal-based anxiolytics were also assessed on the developing zebrafish larvae. Show less
The main focus of the research that makes up this thesis was to translate rodent behavioural assays to larval zebrafish for better time and resource management in biomedical research,... Show moreThe main focus of the research that makes up this thesis was to translate rodent behavioural assays to larval zebrafish for better time and resource management in biomedical research, pharmaceutical research and development. __The larval zebrafish is a useful model in toxicology and drug discovery. However, its predictivity is restricted by compound class. __Light-dark cycle plays an important role in the normal development of the zebrafish embryo, and abnormal lighting regimes during rearing can result in malformations. __The hyperactivity displayed by zebrafish larvae following the onset of sudden darkness is an intrinsic characteristic. Zebrafish larvae quickly habituate with repeated stimuli of onset of darkness with short interstimulus interval. __Zebrafish larvae are able to discriminate colours, and they show a preference for orange and green, but aversion towards red, yellow, blue and black. The larvae also show freezing behaviour in the complex environment which is attenuated with diazepam.. __Zebrafish larvae raised in an abnormal lighting regime changed some aspects of their colour preference, although orange and red remained as preferred and avoided colours respectively. __In short, the zebrafish larvae is a useful complementary animal model in behavioural research amenable to high-throughput screening of compounds and drug discovery Show less
