Chotosan,a Kampo Formula,Ameliorates Hippocampal LTD and Cognitive Deficits in Juvenile-Onset Diabetes Rats

Childhood-onset type 1 diabetes is associated with modest impairments in cognition and has an elevated risk of cognitive decline. Our previous study showed that working memory and hippocampal long-term depression (LTD) were impaired in juvenile-onset diabetes mellitus (JDM) rats. In this study, we investigated the effect of chotosan (CTS), a traditional herbal formula called a Kampo medicine, which has been clinically demonstrated to be effective for the treatment of vascular dementia, on JDM rats. The repeated treatment with CTS (1 g/kg per day) for 3 – 7 days restored spatial working memory and hippocampal LTD in JDM rats. The expression level of NR2B glutamate receptor subunits, but not other glutamate receptor subunits was enhanced in the hippocampus of JDM rats, and repeated treatment with CTS reversed these changes. These results suggest that CTS improves diabetes-induced cognitive deficits by modulating NMDA-receptor subunit expression.