Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment

摘要

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-d-aspartate receptors (NMDAR) and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.