Lead Exposure Induced Neural Stem Cells Death via Notch Signaling Pathway and Gut-Brain Axis

Numerous studies have examined the effects of lead (Pb) on cognitive ability. It is essential for the brain to maintain its functions through the differentiation of neural stem cells into various types of cells. Despite this, it remains unclear how Pb exposure affects neural stem cells and how it does, so the Pb-exposed mice were treated with the Notch inhibitor DAPT after we established the Pb exposure models. Neuronal stem cells and autophagy were assessed by immunofluorescence staining and western blot. The microbiota of the feces was also analyzed using the 16S rRNA amplicon sequencing technique. In this study, we found that Pb exposure caused neural injuries and deficits in neural stem cells, whereas DAPT rescued the damage. With DAPT, Pb-induced autophagy was partially reversed. Exposure to Pb also reduced inflammation and damaged gut barrier function. Furthermore, Pb exposure led to low bacterial diversity, an increase in pathogen abundance, and an unusual mode of interaction. Taken together, this study revealed that damages in neural stem cells contributed largely to cognitive impairment during Pb exposure, and this process was partially dependent on the Notch pathway and gut dysbiosis.