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Glutamate receptor binding in the human hippocampus and adjacent cortex during development and aging
M Johnson1, R H Perry, M A Piggott
1MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
Neurobiology of Aging
|July 1, 1996
Summary
Glutamate receptor binding in the human hippocampus changes significantly during development and aging. These alterations in NMDA, AMPA, and kainate receptors are not linked to normal aging neurodegeneration.
Area of Science:
- Neuroscience
- Neurochemistry
- Developmental Biology
Background:
- The human hippocampus and parahippocampal gyrus undergo significant neurodevelopmental and aging processes.
- Glutamate receptors, including NMDA, AMPA, and kainate, play crucial roles in synaptic plasticity and cognitive functions.
- Understanding age-related changes in these receptors is vital for comprehending brain health and disease.
Purpose of the Study:
- To investigate age-related alterations in NMDA, AMPA, and kainate receptor binding in the human hippocampus and parahippocampal gyrus across the lifespan.
- To determine if these receptor binding changes are associated with normal aging or neurodegenerative processes.
Main Methods:
- Analysis of NMDA (MK801 binding), AMPA (CNQX binding), and kainate binding patterns in post-mortem human brain tissue.
- Study population ranged from 24 gestational weeks to 94 years, encompassing fetal, neonatal, adult, and aged individuals.
- Regional analysis within the dentate gyrus, hippocampus proper, subicular complex, and entorhinal cortex.
Main Results:
- MK801 (NMDA receptor) binding remained relatively stable across the lifespan.
- CNQX (AMPA receptor) binding increased from fetal stages to a peak in neonates/middle age, then declined in specific regions post-maturity.
- Kainate receptor binding showed a marked decline from perinatal to adult stages, with no significant changes in later life.
Conclusions:
- Age-related changes in glutamate receptor binding are region-specific and dynamic during development and aging.
- Transient peaks in receptor binding likely reflect synaptogenesis and pruning, offering insights into developmental disorders.
- The lack of significant receptor binding changes from middle to old age suggests these glutamate receptor subtypes are not implicated in senescent neurodegeneration.