The influences of juvenile diabetes on memory and hippocampal plasticity in rats: improving effects of glucagon-like peptide-1.

Previous studies in children with diabetes found that hyperglycemia induces memory dysfunction. In this study, we investigated memory and synaptic plasticity in streptozotocine (STZ)-induced diabetic rats during the juvenile period. We further investigated the effects of glucagon-like peptide-1 (GLP-1) on the diabetes-induced profiles. STZ (85 mg/kg, i.p.) was administered to 17-day-old Wistar rats to induce type-1 juvenile diabetes mellitus (JDM). In the Y-maze test, JDM rats showed significant impairment of learning and memory, which were improved by GLP-1 (7-36) amide (1 microg/5 microl/rat, i.c.v.). Extracellular recording at Schaffer collateral synapses in the CA1 region of hippocampal slices showed that long-term potentiation and paired-pulse facilitation in JDM rats were similar to age-matched control rats. However, the input-output relation was strengthened, and long-term depression (LTD) and responses of N-methyl d-aspartic acid through NR2B subunits were weakened in the JDM rats. GLP-1 (7-36) amide (100 nM) increased the magnitude of LTD and the responses through NR2B in the JDM rats. These results indicate that the lack of LTD and NR2B responses may contribute to impairment of memory associated with JDM, suggesting the potential usefulness of GLP-1 in the treatment of memory dysfunction in JDM.