AUTORADIOGRAPHIC COMPARISON OF THE DISTRIBUTION OF [H-3] MK801 AND [H-3] CNQX IN THE HUMAN CEREBELLUM DURING DEVELOPMENT AND AGING

The autoradiographic distribution of N-methyl-D-aspartate (NMDA) and - a-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid/quisqualate (AM PA/QUIS) receptors was determined in cerebellum obtained at autopsy fr om 37 human individuals, aged from 24 weeks gestation to 95 years. [H- 3]MK801 was used to label the NMDA receptor and [H-3]CNQX to label the AMPA/QUIS receptor. AMPA/QUIS receptors were concentrated in the cere bellar molecular layer, and NMDA receptors in the granular layer. Sign ificant (3- to 4-fold) increases in binding were seen for both ligands from the fetal to neonatal periods in the molecular layer (CNQX) and in both molecular and granular layers (MK801). MK801 binding in the mo lecular layer continued to increase with age up to the tenth decade an d together with binding in the granular layer, increased 2-fold betwee n 10-40 years. The Purkinje cell layer was negative for MK801 binding until the 6-7th decade when it became positive. [H-3]CNQX binding in t he molecular layer increased significantly with age between the fetal period and the tenth decade, whereas in the granular layer binding inc reased from neonate to 40 years, but then decreased significantly from 60 years to the the tenth decade. Lamination of the molecular and gra nular layers was absent during the fetal period and appeared with both ligands during the neonatal period. These marked differences in age-r elated expression of ligand binding sites in the granular layer during development and aging are of potential significance in relation both to selective vulnerability to ischaemia, and synaptic plasticity and r emodelling related to neuronal loss in senescence.