Proteomic analysis of hippocampus in relation to effects of yokukansan on diabetic model mice showing dementia

Diabetes is at an increased risk for development of dementia and effective treatments for diabetes-induced dementia are required with urgency. Yokukansan, a Kampo medicine, is used clinically to treat several neurological conditions including dementia. In this study, we aimed to show the effects of yokukansan on learning and memory functions in diabetes-induced dementia and to clarify the molecular mechanisms inducing the effects in the hippocampus of yokukansan- and non-treated diabetic model mice. Morris water maze test showed that yokukansan admin-istration significantly improved learning and memory functions of diabetic model mice. In the proteomic analysis, significant changes in expression of 10 (4 up- and 6 down-regulated) proteins and 8 (3 up- and 5 down-regulated) phosphoproteins were observed in the hippocampus of yokukansan-treated diabetic model mice. These identified proteins and phosphoproteins could be functionally classified as neuronal development, cellular cytoskeleton, energy metabolism, oxi-doreductase, protein deubiquitination, proton transport, and chaperone. Additionally, western blotting validated the changes in CAPZB, tubulin beta-5 chain, and LDHB. Taken together, these results showed that yokukansan improved learning and memory functions in mice with diabe-tes-induced dementia, underlying the changed expression of proteins and phosphoproteins in the hippocampus. We propose that yokukansan could be effective for care of diabetes-induced de-mentia.