Effects of Elevated D-Glucose Concentrations on AMPA and NMDA Re ceptor Activity in Modeled Hyperglycemia in Brain Slices

The effects of various D-glucose concentrations (0.5; 1; 3; 5; 7; 10; 12; 14; 17; 20; 22; and 25 mM) were studied using brain slices of the rat olfactory cortex to determine changes in the activities of AMPA and NMDA ionotropic glutamatergic mechanisms. The dependence of the amplitudes of the AMPA and NMDA potentials on D-glucose concentrations was dome-shaped. Lower concentrations (0.5; 1; 3; 5 mM) caused a progressive increase in the amplitudes of AMPA and NMDA potentials. Under D-glucose concentra tions in the extracellular medium of 7 and 10 mM, the amplitudes of AMPA and NMDA potentials were maximal and stable. Under a D-glucose concentration of 14 mM, the activities of AMPA and NMDA mechanisms decreased and, following a further increase in carbon, were irreversibly blocked. Long-term post-tetanic potentiation (model of non-associative learning) developed only at a D-glucose concentration of 10 mM. Heat shock protein (Mw70 kDa) protected the activities of AMPA and NMDA mechanisms from the negative effects of high hyperglycemic D-glucose concentration of 14 mM. The data obtained indicate the response of AMPA and NMDA mechanisms during the development of hyperglycemia. This model can be used to search for substances to protect neuronal mechanisms in the nervous tissue during the develop ment of hyperglycemic diabetes mellitus.