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N-methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain.

R A Gonzales1, L M Brown, T W Jones

  • 1Institute for Neuroscience, University of Texas, Austin.

Neurobiology of Aging
|May 1, 1991
PubMed
Summary
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Aging impairs N-Methyl-D-aspartate (NMDA) receptor function in rat brain regions. NMDA receptor-mediated inhibition and neurotransmitter release significantly decrease with age, particularly in senescent rats.

Area of Science:

  • Neuroscience
  • Aging Research
  • Neuropharmacology

Background:

  • N-Methyl-D-aspartate (NMDA) receptors play crucial roles in synaptic plasticity and neurotransmission.
  • Age-related changes in brain function are well-documented, but specific alterations in NMDA receptor activity remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of aging on NMDA receptor function in specific rat brain regions.
  • To assess age-dependent alterations in NMDA receptor-mediated signaling pathways.

Main Methods:

  • Studied NMDA receptor function in Fischer 344 rats across three age groups (young, middle-aged, senescent).
  • Assessed NMDA-induced inhibition of muscarinic-stimulated phosphoinositide hydrolysis in the hippocampus.
  • Measured NMDA-stimulated release of [3H]norepinephrine and [3H]dopamine from hippocampal, cortical, and striatal slices.

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Main Results:

  • NMDA receptor-mediated inhibition of hippocampal phosphoinositide hydrolysis was significantly reduced in middle-aged (25%) and senescent (53%) rats.
  • Maximal NMDA-stimulated [3H]norepinephrine release decreased with age in hippocampal slices.
  • Cortical NMDA receptor function showed a 23% reduction in senescent rats, and striatal [3H]dopamine release was lower in senescent rats.

Conclusions:

  • Aging leads to a significant, age-dependent decline in NMDA receptor function across multiple brain regions.
  • These findings suggest that age-related alterations in NMDA receptor activity may contribute to cognitive and motor deficits observed in aging.