Three-Dimensional (3D) Cellular Models: Next-Generation Tools in Neurotoxicology Research

Animals have long been utilized to understand the impact of environmental factors contaminants and chemicals on the brain function. While they remain a valuable tool to predict the outcome in humans, they are resource-intensive, constrained by ethical concerns, and often fails to fully predict human-specific responses. In vitro human cellular models offering some advantages but still lack the intricate architecture and microenvironment of human neural tissue. 3D cellular models provide an interphase between traditional in vitro methods and in vivo systems. Derived from human cells, 3D models, including organoids, spheroids, and advanced bioengineered platforms like "human-on-a-chip" systems, can better replicate the cellular heterogeneity, spatial organization, and functional dynamics of the human brain.

Since past decades, the field of neurotoxicology is undergoing a transformative shift, driven by advancements in three-dimensional (3D) cellular models. These next-generation tools hold the promise of providing ethically sustainable, human-relevant models for predicting neurotoxicity with enhanced accuracy and reliability. Despite their promise, the implementation of 3D cellular models in neurotoxicology remains in its early stages. Key challenges include ensuring reproducibility and verify their predictive sensitivity to xenobiotics. Addressing these challenges will be critical for fully realizing the potential of 3D models in advancing neurotoxicology research.

We invite researchers to contribute to this Research Topic, showcasing original research articles, reviews (including systematic and mini reviews), methods, editorials, opinions, and perspectives on 3D cellular models in neurotoxicology. This collection aims to highlight the transformative impact of 3D cellular models in guiding safer chemical design, therapeutic interventions, and our understanding of neurotoxicology.

Topics of interest include, but are not limited to:
• 3D cellular models used to predict xenobiotic induced neurotoxicity
• Role of various neural cells and inter-cellular communication capabilities in 3D milieu to study neurotoxic mechanisms
• Advancement in 3D models to ensure high reproducibility and/or predictivity in neurotoxicity or disease
• Deciphering the neurotoxic mechanism of novel compounds using 3D models
• 3D brain disease models and their interaction with chemicals to understand their impact to disease progression
• 3D brain disease models to understand the early emergence of neurodegenerative conditions by environmental exposure
• Recent advances in bioengineering, imaging, and multi-omics technologies enhancing the utility of 3D models, enabling high-throughput screening and in-depth mechanistic studies