IMPAIRED MODULATION OF AMPA RECEPTORS BY CALCIUM-DEPENDENT PROCESSES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The mechanisms by which diabetes impairs cognitive function are not we ll-established. In the present study, we determined the electrophysiol ogical and biochemical nature of disturbances in the mechanism of long -term potentiation (LTP) in diabetic rats. As previously reported, the administration of streptozotocin (STZ) was found to reduce the magnit ude of LTP in the CA1 region of the hippocampus, while the same treatm ent did not interact with the capacity of the hippocampus to generate long-term depression induced by low-frequency stimulation. In addition , STZ treatment did not modify the component of excitatory postsynapti c potentials mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, suggesting that NMDA receptor functio n remained intact in STZ-treated slices. At the biochemical level, the capacity of calcium to increase [H-3]( RS)-alpha-amino-3-hydroxy-5-me thylisoxazole propionic acid (H-3-AMPA) binding to glutamate/AMPA rece ptors in rat brain tissue sections was markedly affected in most regio ns of the hippocampus of STZ-treated rats. Moreover, changes in H-3-AM PA binding properties elicited by both exogenous phospholipase A, and melittin, a potent activator of endogenous phospholipases, were also a ltered in synaptoneurosomes from diabetic rats. Taken together, the pr esent data suggest that the loss of LTP maintenance in STZ-treated rat s is more likely the result of disruption of calcium-dependent process es that are suspected to modulate postsynaptic AMPA receptors during s ynaptic potentiation. Understanding the biochemical factors participat ing in the impairment of AMPA receptor modulation might provide import ant clues revealing the very basis of memory deficits in diabetes. (C) 1997 Elsevier Science B.V.