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In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
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Pervasive environmental chemicals impair oligodendrocyte development.

Erin F Cohn1, Benjamin L L Clayton1, Mayur Madhavan1

  • 1Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

Biorxiv : the Preprint Server for Biology
|February 17, 2023
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Summary

Common household chemicals like disinfectants and flame retardants can harm developing brain cells called oligodendrocytes. This study identifies specific chemical risks to neurodevelopment in children.

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Area of Science:

  • Neuroscience
  • Toxicology
  • Developmental Biology

Background:

  • Environmental chemical exposure poses risks to neurodevelopment.
  • Oligodendrocytes, crucial for nerve function, are vulnerable during development.
  • Limited assessment of environmental chemicals for oligodendrocyte developmental toxicity exists.

Approach:

  • Utilized high-throughput screening and human cortical brain organoids.
  • Identified two classes of environmental chemicals disrupting oligodendrocyte development.
  • Investigated mechanisms including cytotoxicity and maturation arrest.

Key Points:

  • Quaternary compounds (disinfectants, softeners) are cytotoxic to oligodendrocytes via the integrated stress response.
  • Organophosphate flame retardants (furniture, electronics) prematurely arrest oligodendrocyte maturation.
  • Both chemical classes impaired human oligodendrocyte development in 3D organoid models.

Conclusions:

  • Identified specific toxicological vulnerabilities in oligodendrocyte development.
  • Highlighted common household chemicals posing high exposure risks to children.
  • Results warrant further investigation into the health impacts of these chemicals.