D-Fructose Exposure Impairs Neuronal Development in Mouse Neural Stem Cells.

Maternal obesity and a Western diet high in fat and sugars are increasing worldwide and may contribute to rising neurodevelopmental and neurobehavioral disorders in offspring. Both human and animal studies link these factors to adverse outcomes. However, the cellular mechanisms driving altered early-life neurogenesis, particularly in the hippocampus, remain unclear. To assess fructose effects on neural stem cell (NSC) differentiation and neuronal morphology, hippocampal NSCs from E12.5 C57BL/6 mouse embryos were cultured and treated with fructose (8.75 or 12.5 mM) for 7 days. Neuronal and astrocyte populations, along with neuronal morphology, were analyzed by immunofluorescence, and protein expression was assessed by Western blot. Fructose treatment significantly reduced neuronal and increased astrocyte counts, leading to a decreased neuron-to-astrocyte ratio compared to controls. These findings were supported by decreased MAP2 (neuronal) and increased GFAP (astrocyte) protein expression. Furthermore, fructose also significantly reduced neurite lengths without affecting neurite number. Morphological analysis revealed decreased soma size, reduced area/perimeter, and altered soma area-to-perimeter ratios, indicating impaired structural integrity. Thus, fructose exposure shifts NSC differentiation toward an astroglial lineage while suppressing neuronal development and impairs neuronal growth and structural complexity. Future studies are necessary to determine the influence of these cellular changes on synaptic plasticity and learning, as well as memory.