Early F-53B Exposure Induces Autism Spectrum Disorder-like Hypomyelination and Oligodendrocytes-Derived Exosomal...

Area of Science:

• Neuroscience
• Toxicology
• Developmental Biology

Background:

• Epidemiological studies suggest a link between prenatal exposure to chlorinated polyfluorinated ether sulfonate (F-53B) and neurodevelopmental deficits associated with autism spectrum disorder (ASD).
• The precise mechanisms by which F-53B induces ASD-like pathology and impairs oligodendrocyte function are not fully understood.

Purpose of the Study:

• To investigate the neurodevelopmental effects and underlying mechanisms of prenatal F-53B exposure in Sprague-Dawley rats.
• To compare F-53B-induced outcomes with a valproic acid model of ASD.

Main Methods:

• Sprague-Dawley rats were exposed to F-53B (0, 8, 80, 800 μg/kg/d) from preconception through postweaning.
• Neurobehavioral assessments, neuropathological examination, and analysis of oligodendrocyte-derived exosomes (ODEXs) were performed.
• Proteomic profiling of ODEXs and molecular docking were utilized to identify molecular targets.

Main Results:

• F-53B crossed the blood-brain barrier, leading to ASD-like neurobehaviors (social deficits, stereotypic behaviors, memory impairment) and hypomyelination in offspring.
• F-53B exposure delayed oligodendrocyte maturation and disrupted neuronal mitochondrial structure.
• ODEXs from exposed rats showed suppressed ATP synthesis-related proteins, including chromodomain helicase DNA binding protein 8 and ATP citrate lyase, which F-53B could bind to.

Conclusions:

• Oligodendrocyte-derived exosome-mediated disruption of ATP synthesis is a key mechanism in F-53B-induced ASD-like pathology.
• The findings suggest that F-53B neurotoxicity warrants reevaluation, particularly concerning its use as an alternative to perfluorooctanesulfonate.