The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats.

ObjectivesConsidering the deleterious effect of A1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in A1-42-injected Wistar rats. MethodsThe rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated A1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis. Key findingsThe Western blot revealed that A1-42-injected rats had significantly low levels of synaptophysin as compared to sham control. Phloretin pretreatment significantly protected the presynaptic protein synaptophysin against the effects of A1-42. There were no significant changes in the levels of PSD95 between different groups. The IHC findings showed that A1-42 significantly reduced the Ki67 and DCX in the dentate gyrus as compared to sham control. However, phloretin significantly improved the number of Ki67- and DCX-positive neurons in the dentate gyrus region as compared to A1-42 group. ConclusionsThis study demonstrated the protective effect of phloretin on synaptophysin and adult neuronal proliferating cells in A1-42-injected rats. The encouraging findings highlight the potential of phloretin as a dietary supplement targeting key therapeutic mechanisms in neurodegenerative disorders such as AD.