Decreased density, but not number, of N-methyl-D-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats.
Aging is associated with reduced rates of kindling and spatial learning. Blockade of N-methyl-D-aspartate (NMDA) receptors in young animals produces effects similar to those of aging. These findings raise the possibility that age-dependent reductions in neuronal plasticity are the consequence of decreased NMDA receptor-mediated neurotransmission. Conceivably this reduction could be due to an alteration in the NMDA receptor itself. To test this idea we quantified ligand binding to 3 distinct sites on the NMDA receptor/channel complex in hippocampal membranes prepared from 3- and 24-month-old Fischer-344 rats. The binding parameters of the NMDA, glycine and non-competitive antagonist (A.K.A. phencyclidine) sites on the NMDA receptor/channel complex were examined using [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP), [3H]glycine and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP), respectively. Aging produced no change in the affinity or stoichiometry of the binding sites. Aging was associated with a 30% reduction in the density of each of the 3 binding sites (when expressed as sites/mg membrane protein). However, this reduction in receptor density was the consequence of increased protein content in the hippocampus of aged animals, not a reduction in the number of binding sites. These findings suggest that a selective alteration in the NMDA receptor/channel complex itself does not account for the age-dependent reductions in neuronal plasticity.
Bonhaus
D W
DW
Department of Pharmacology, Duke University Medical Center, Durham, NC 27705.
Perry
W B
WB
McNamara
J O
JO
D000375:Aging / Q000378:metabolism*; D000818:Animals; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D009943:Organophosphorus Compounds / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine; D009435:Synaptic Transmission / Q000502:physiology
D009943:Organophosphorus Compounds; D010879:Piperazines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; C065286:SDZ EAA 494; C012058:tenocyclidine; D010622:Phencyclidine; D005998:Glycine