AGE-RELATED-CHANGES IN EXPRESSION OF AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBUNITS - IS CALCIUM-PERMEABILITY ALTERED IN HIPPOCAMPAL-NEURONS

Age-related decline of cognition and memory, in humans and other anima ls, appears to be associated with neuronal loss.(6,9,28) Experimental and clinical evidence has shown that the hippocampal formation is one of the brain regions most vulnerable to the ageing process.(1,2,10,11, 13,17,18,20,23) Because excess of glutamate is neurotoxic to hippocamp al neurons,(3) abnormalities in glutamate neurotransmitter function ma y play a crucial role in neurodegenerative disorders, especially in co njunction with brain ageing.(8,14) We have used in situ hybridization to study the expression of the two major alpha-amino-3-hydroxy-5-methy l-4-isoxazole propionic acid (AMPA)-selective glutamate receptor subun its, involved in the control of calcium permeability in the young adul t and aged rat hippocampus. We show that the levels of messenger RNA e ncoding the AMPA-selective glutamate receptor subunit-1 (GluR1 or GluR A) and AMPA-selective glutamate receptor subunit-2 (GluR2 or GluRB) ar e highest in the dentate gyrus, followed by the CA1 anti CA3 hippocamp al subfields. We also show that the levels of both messenger RNAs decr ease differentially with age in all subfields of the hippocampus. Fina lly, the GluR1/GluR2 messenger RNA ratios increase in the aged hippoca mpus, particularly in the CA3 subfield, suggesting that altered calciu m homeostasis may contribute to age-related neuronal death.