Adverse Outcome Pathway on Binding to voltage gate sodium channels during development leading to cognitive impairment

Iris Mangas, Antonio F. Hernandez, Kevin Crofton, Mary Gilbert, Martin Paparella, Anna Price, Tim Shafer, Laura Martino, Martina Panzarea and Andrea Terron

No 36, OECD Series on Adverse Outcome Pathways from OECD Publishing

Abstract: This adverse outcome pathway links the binding of xenobiotics to voltage gate sodium channels (VGSCs) during development, to cognitive impairment. The binding of xenobiotics to VGSCs may lead to disruption of action potential generation and consequently to an alteration in neurotransmission. Neurotransmitter release is essential for neural activity and neural activity is critical for normal brain development. Therefore, chemicals that bind with VGSCs have the potential to cause adverse effects on the developing brain. This AOP focuses on the hippocampus because of its well-known ties to cognition, and downstream outcome of concern for many chemical exposures. This AOP is referred to as AOP 442 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki): https://aopwiki.org.

Date: 2025-06-26
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