Effects of post-mortem delay on subunits of ionotropic glutamate receptorsin human brain

The effect of post-mortem delay on the stability of the protein subunits th at combine to form NMDA and AMPA type glutamate receptors has been assessed in samples of human brain tissue. While most of the subunits (i.e. GluR1, GluR2/3, GluR4, NR1) appear to be stable for up to 18 h post-mortem, the NR 2A and NR2B subunits appear to be proteolyzed rapidly following death. Thes e results an consistent with the concept that the proteolytic products of N R2A and NR2B, although at smaller molecular sizes than the full-length prot ein, are all identifiable on Western blots. Thus, a method is proposed that allows for the estimation of the levels of these labile proteins even in s amples obtained up to 18 h post-mortem. Using this method we have estimated the levels of all AMPA and NMDA receptor subunits; in selected (i.e. hippo campus. frontal and entorhinal cortex) brain tissue samples obtained from c ontrol patients and patients who have died with Alzheimer's disease. Modest decreases in NMDA receptor subunits NR1, NR2A, and NR2B were found in the hippocampus and in frontal cortex while little or no change in any of these subunits were documented in entorhinal cortex. Subunits for AMPA receptors (GluR1, GluR2/3, and GluR4) appeared to show a generalized decrease in all these tissues. As a surrogate marker for overall decreases due to generali zed neuronal cell death, levels of neuron-specific enolase were measured in all tissues and were found to be neatly identical in control and Alzheimer 's brains. (C) 2000 Elsevier Science B.V. All rights reserved.