Editor's Highlight: Evaluation of a Microelectrode Array-Based Assay for Neural Network Ontogeny Using Training Set...

Area of Science:

• Neuroscience
• Toxicology
• Assay Development

Background:

• Thousands of environmental compounds lack developmental neurotoxicity (DNT) hazard characterization.
• Rapid screening methods are crucial for evaluating DNT risks of these compounds.
• Assays for key neurodevelopmental processes, like neural network formation, are needed.

Purpose of the Study:

• To develop and validate an assay for assessing DNT potential by measuring neural network formation.
• To evaluate the effects of known compounds on neural network activity using microelectrode arrays (MEAs).
• To identify key parameters indicative of DNT hazard in developing neural networks.

Main Methods:

• Primary rat cortical cells (0-24h old) were cultured on 48-well MEA plates.
• Cells were exposed to acetaminophen, bisindolylmaleimide-1 (Bis-1), domoic acid, mevastatin, sodium orthovanadate, and loperamide for 12 days.
• Spontaneous electrical activity was recorded on MEAs, and cell viability was assessed.

Main Results:

• Network activity parameters (e.g., mean firing rate, burst rate) increased from day 5 to 12.
• Random Forest analysis identified temporal firing correlation, MFR, BR, and burst characteristics as key discriminators.
• Most tested compounds, except acetaminophen, altered network activity parameters concentration-dependently, with some effects observed below cytotoxic levels.

Conclusions:

• Domoic acid and sodium orthovanadate induced DNT-related changes without cytotoxicity.
• Bis-1, mevastatin, and loperamide showed effects at sub-cytotoxic concentrations.
• The developed MEA-based assay is suitable for screening compounds for developmental neurotoxicity hazards.