The toxifin platform: advancing high-throughput screening and mechanistic insights for developmental neurotoxicants using the zebrafish model

Ended Project Grant Awarded

Award ID
R43ES036386
Recipient
Awarding agency
Obligated
$296,420

Award facts

Assistance listing
93.113 Environmental Health
Completion date
Place of performance
Eugene, OR 97402, USA

Award details come from USAspending.gov.

Description

Abstract
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.

Quick answers

Who received award R43ES036386?

R43ES036386 was awarded to Invivo Biosystems, Inc. by National Institute of Environmental Health Sciences (National Institutes of Health) on May 1, 2024.

How much is award R43ES036386 worth?

$296,420 has been obligated on R43ES036386.

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