Rapamycin Pretreatment Attenuates High Glucose-induced Alteration of Synaptic Transmission in Hippocampal Dentate Gyrus Neurons.

Diabetic neuropathy is one of the most common complications in patients with diabetes and leads to cognitive impairment. It is suggested that protracted hyperglycemia is the main trigger of cognitive deficits in diabetes and causes hippocampal abnormalities. Rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can significantly ameliorate cognitive deficits in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington disease. We employed whole-cell patch clamping to examine the effects of rapamycin on neuronal electrophysiological characteristics of the hippocampal dentate gyrus in mice under the condition of high glucose. We recorded the action potentials (APs) and the miniature excitatory postsynaptic currents (mEPSCs) of dentate gyrus neurons. We found that high glucose increased the half-width, the duration and decreased the peak amplitude of Aps as well as the inter-event interval (IEI) of mEPSCs in hippocampal dentate gyrus neurons. However, rapamycin pre-treatment reversed the changes induced by high glucose. Moreover, we demonstrated that rapamycin pre-treatment reversed the down-regulation of postsynaptic density protein 95 (PSD-95) expression caused by high glucose. Therefore, pre-treatment with rapamycin could ameliorate high glucose-induced alteration of synaptic transmission in the hippocampal dentate gyrus.