Established and emerging new approach methodologies in neuroscience

Area of Science:

• Neuroscience
• Toxicology
• Drug Development
• In Vitro and In Vivo Models

Background:

• Growing demand for ethical, human-relevant, and efficient alternatives to animal testing.
• Neurological disease complexity poses challenges for fully replacing animal models.
• New Approach Methodologies (NAMs) are crucial for safety assessment and drug discovery.

Purpose of the Study:

• To review the current landscape of NAMs in neuroscience research.
• To examine various models, including 2D/3D in vitro systems and zebrafish.
• To compare human, mouse, and zebrafish brain organoids for their utility.

Main Methods:

• Review of existing literature on NAMs in neuroscience.
• Analysis of different in vitro (2D cell cultures, brain organoids) and in vivo (zebrafish) models.
• Comparative assessment of model strengths, limitations, and applicability in research.

Main Results:

• Diverse NAMs exist, including cell cultures, brain organoids (human, mouse, zebrafish), and zebrafish models.
• Human and mouse brain organoids show promise but are limited by cost and time for high-throughput screening.
• Zebrafish models offer faster, cost-effective, and scalable platforms for early-phase screening and toxicology.

Conclusions:

• NAMs are vital for advancing ethical and efficient safety assessment and drug discovery in neuroscience.
• Integrating complementary models like brain organoids and zebrafish can create robust research pipelines.
• Future directions focus on optimizing these integrated systems for early-phase toxicity testing and drug development.