Fe 3 O 4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice.

Aging is a process associated with blood-brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe 3 O 4 nanozymes on neurogenesis have rarely been studied. This study examined the effects of Fe 3 O 4 nanozymes on neuronal differentiation in the dentate gyrus (DG) and BBB integrity of D-galactose-induced aged mice. Long-term treatment with Fe 3 O 4 nanozymes (10 μg/mL diluted in ddH 2 O daily) markedly increased the doublecortin (DCX) immunoreactivity and decreased BBB injury induced by D-galactose treatment. In addition, the decreases in the levels of antioxidant proteins including superoxide dismutase (SOD) and catalase as well as autophagy-related proteins such as Becin-1, LC3II/I, and Atg7 induced by D-galactose treatment were significantly ameliorated by Fe 3 O 4 nanozymes in the DG of the mouse hippocampus. Furthermore, Fe 3 O 4 nanozyme treatment showed an inhibitory effect against apoptosis in the hippocampus. In conclusion, Fe 3 O 4 nanozymes can relieve neuroblast damage and promote neuroblast differentiation in the hippocampal DG by regulating oxidative stress, apoptosis, and autophagy.