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.