The ToxiFin Platform: Advancing High-Throughput Screening and Mechanistic Insights For Developmental Neurotoxicants Using the Zebrafish Model - SUMMARY
With increasing rates of neurodevelopmental disorders in children, there is an urgent need to assess the
impact of household, agricultural, and industrial chemicals on neurological development. Conventional rodent
testing is costly and time-consuming, hindering widespread adoption. This study aims to develop a
high-throughput and sensitive screening platform for developmental neurotoxicity (DNT) testing, making it
accessible to manufacturers, agricultural users, waste generators, and local governments. The results of
expanded DNT testing could inform governmental policies, improve environmental clean-up efforts, and guide
the development of safer alternatives to neurotoxic chemicals.
Current methods rely on treating rat mothers during pregnancy and lactation, limiting testing to a fraction of the
thousands of chemicals present in the environment. Moreover, these methods may not detect subtle effects on
synapse formation and circuitry performance. To address these limitations, this study proposes the ToxiFin
platform, utilizing the zebrafish model for cost-effective and high-fidelity DNT screening. This platform
incorporates automated screening and analysis methods to efficiently provide endpoints relevant to circuit
formation, circuit function, and brain organization.
Aim 1 focuses on developing a high-throughput screen for neural circuit formation by engineering a transgenic
zebrafish line with bioluminescent signals when synapses are formed. Aim 2 aims to develop an efficient and
scalable screen for assessing developmental neurotoxic effects on neural circuit function and central nervous
system organization. This will be achieved through screening behaviors associated with neurodevelopmental
health, from embryo to adult stages.
The proposed platform has the potential to assess a broader range of chemicals for DNT, diversify endpoints
for detection, and enable effective risk assessment, regulation, and intervention strategies. By utilizing the
zebrafish model, this study offers a cost-effective and efficient alternative to conventional rodent testing
methods, with implications for public health and environmental protection.
