Insulin treatment prevents the increase in D-serine in hippocampal CA1 area of diabetic rats.

PURPOSE:Diabetes is a high risk factor for dementia. Employing a diabetic rat model, the present study was designed to determine whether the content of D-serine (D-Ser) in hippocampus is associated with the impairment of spatial learning and memory ability. METHODS:Diabetes was induced by a single intravenous injection of streptozotocin (STZ). The insulin treatment began 3 days after STZ injection. RESULTS:We found that both water maze learning and hippocampal CA1 long-term potentiation (LTP) were impaired in diabetic rats. The contents of glutamate, D-Ser, and serine racemase in the hippocampus of diabetic rats were significantly higher than those in the control group. Insulin treatment prevented the STZ-induced impairment in water maze learning and hippocampal CA1-LTP in diabetic rats and also maintained the contents of glutamate, D-Ser, and serine racemase at the normal range in hippocampus. CONCLUSIONS:These results suggest that insulin treatment has a potent protection effect on CA1-LTP, spatial learning and memory ability of the diabetic rats in vivo. Furthermore, insulin may take effect by inhibiting the overactivation of N-methyl-d-aspartate receptors, which play a critical role in neurotoxicity.