Neuroactive drugs in the aquatic environment – understanding their mixture effects in fish using network biology approaches

Theme: Environmental Hazards & Pollution

Primary Supervisor:

Luigi Margiotta-Casaluci

Division of Analytical, Environmental & Forensic Sciences, KCL

Luigi Margiotta-Casaluci's Profile Picture

Secondary Supervisor:

Stephen Sturzenbaum

Division of Analytical, Environmental & Forensic Sciences, KCL

Stephen Sturzenbaum's Profile Picture

Project Description:

The pioneering research carried out by Brooks and collaborators in the early 2000s revealed for the first time the widespread presence of the antidepressant Prozac in American rivers. Since then, numerous studies have demonstrated that several psychoactive pharmaceuticals can be routinely detected in aquatic ecosystems and within aquatic organisms. Many pharmacological targets of these pharmaceuticals are evolutionary and functionally conserved in wildlife (especially in fish); therefore, it is plausible to hypothesise that exposure to psychoactive pharmaceuticals may cause behavioural alterations of wildlife as it does in humans. Our previous research has tested and validated this hypothesis for several compounds, including the antidepressant fluoxetine, the anxiolytic oxazepam, and the opioid analgesic tramadol.

Most environmental research on pharmaceuticals in the environment is carried out on individual compounds. However, a recent analysis performed in our laboratory has demonstrated that more than 200 neuroactive pharmaceuticals (i.e., acting on central nervous system targets) are prescribed every day in England. This observation raises the concern that this complex mixture of drugs may perturb central nervous system physiology and wildlife behaviour even if the environmental levels of the individual compounds are considered safe.

The aim of this project is to address this scientific challenge by integrating innovative network pharmacology approaches to predict with high precision the dynamic risk associated with exposure to complex mixtures of neuroactive drugs, and to validate those predictions using (non-protected) zebrafish early life stages genetically engineered with CRISPR-Cas9.

Policy Impact of Research:

Despite the growing concerns about the potential ecological effects of chemical-induced behavioural alterations in wildlife, the regulatory interpretation of behavioural ecotoxicology studies remains largely uncertain. This project will provide a novel pharmacology-informed framework to interpret the environmental risk of dynamic mixtures of neuroactive pharmaceutical compounds and enhance wildlife protection.

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