GLUTAMATE-RECEPTOR BINDING IN THE HUMAN HIPPOCAMPUS AND ADJACENT CORTEX DURING DEVELOPMENT AND AGING

Distinct patterns of age-related alterations in NMDA (MK801 binding) a nd non-NMDA, AMPA (CNQX), and kainate binding have been identified in human hippocampus and parahippocampal gyrus in normal individuals with no evidence of degenerative brain disease ranging in age from 24 gest ational weeks to 94 years. Whereas MK801 binding did not alter substan tially over this age range, CNQX binding rose from low levels in the f etus to maximum levels between neonate and middle age, and kainate bin ding declined extensively from the perinatal to adult stage. Following maturity, there were no significant changes in kainate binding, altho ugh MK801 binding increased in CAI and CA3 and CNQX binding declined i n several regions, particularly CA2 and subiculum. For each receptor b inding the timing of these fluctuations ocurring during development an d aging varied within different regions of the dentate gyrus, hippocam pus proper, subicular complex, and entorhinal cortex examined. The tra nsient peaks of receptor binding are likely to reflect processes of sy naptogenesis and pruning and may provide clues regarding the role of t he different glutamate receptor subtypes in various pathologies of the hippocampus and adjacent cortex associated with developmental disorde rs (of genetic origin or due to perinatal trauma or insult). The absen ce of substantial changes in any subtype examined from middle to old a ge suggests alterations in transmitter binding to these glutamate rece ptors are not involved in senescent neurodegeneration.