Effects of ascorbic acid on myelination in offspring of advanced maternal age.

Abstract

Myelination is the process by which oligodendrocytes ensheath axons to form myelin sheaths. Myelination is a crucial aspect of brain development and is closely associated with central nervous system abnormalities. However, previous studies have found that advanced maternal age might affect the myelination of offspring, potentially through the pathway of disrupting DNA methylation levels in the offspring's hippocampus. Current research has demonstrated that ascorbic acid can promote hydroxymethylation to reduce methylation levels in vivo. This study aims to verify the relationship between ascorbic acid and myelination, as well as the specific mechanism involved. Initially, oligodendrocyte differentiation was observed using immunofluorescence and Western blot. Myelination was assessed through Luxol Fast Blue staining, Glycine silver staining, immunofluorescence, and transmission electron microscopy. The demethylation level of oligodendrocyte progenitor cells was detected by immunofluorescence co-expression of OLIG2 and DNA hydroxylase ten-eleven translocation 1 (TET1), TET2, and TET3. Our study found that advanced maternal age could impair myelination in the hippocampus and corpus callosum of offspring. Ascorbic acid intervention may induce TET1 and TET2-mediated hydroxymethylation to ameliorate myelination disorders, promote myelination and maturation, and reverse the effects of advanced maternal age on offspring.