Sominone improves memory impairments and increases axonal density in Alzheimer's disease model mice, 5XFAD.

Previously we showed that steroidal sapogenin, sominone improved memory after a single i.p. injection into normal mice. However, it had not been reported that sominone could recover memory deficits in a severe Alzheimer's disease (AD) model animal. Therefore, we aimed to investigate that sominone improved memory impairments in the 5XFAD mouse, model for AD. In the current study, we used sominone that we had synthesized. 5XFAD mice were given 10 μmol/kg sominone intraperitoneally for 9 days. In addition to object recognition memory, axonal density, amyloid plaque number, and activated microglia in the brain were evaluated. Sominone treatment significantly improved object recognition memory compared with vehicle control treatment. Sominone treatment significantly enhanced axonal densities in the frontal cortex and parietal cortex but had no effects on amyloid plaque number and activated microglia. In cultured cortical neurons, the axonal length was significantly reduced by Aβ(1-42) treatment. However, that was markedly recovered 5 days after the treatment with 1 μM sominone. Neuronal loss was not observed in the cortex and hippocampus of 5XFAD mice at 6-8 months of age. These results suggest that memory deficits in AD may be improved by sominone independently of reducing amyloid plaques and neuroinflammation.