Pervasive environmental chemicals impair oligodendrocyte development.
Erin F CohnBenjamin L L ClaytonMayur MadhavanKristin A LeeSara YacoubYuriy FedorovMarissa A ScavuzzoKatie Paul FriedmanTimothy J ShaferPaul J TesarPublished in: Nature neuroscience (2024)
Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable, as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds' impacts on human health.
Keyphrases
- human health
- high throughput
- risk assessment
- endothelial cells
- healthcare
- type diabetes
- pregnant women
- metabolic syndrome
- dna methylation
- mass spectrometry
- young adults
- palliative care
- cell proliferation
- induced apoptosis
- genome wide
- endoplasmic reticulum stress
- electronic health record
- cell cycle arrest
- cell death
- gestational age
- signaling pathway
- single cell
- health insurance
- pi k akt
- drug induced