Decreased density, but not number, of N-methyl-D-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bonhaus, DW; Perry, WB; McNamara, JO

Published Date

  • November 5, 1990

Published In

Volume / Issue

  • 532 / 1-2

Start / End Page

  • 82 - 86

PubMed ID

  • 2178039

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/0006-8993(90)91745-3


  • eng

Conference Location

  • Netherlands