GABAA and alpha-amino-3-hydroxy-5-methylsoxazole-4-propionate receptors are differentially affected by aging in the rat hippocampus

J Biol Chem. 2000 Jun 30;275(26):19585-93. doi: 10.1074/jbc.M000700200.

Abstract

We have investigated the age-dependent modifications in the expression of eight different subunits of the gamma-aminobutyric acid, type A (GABA(A)) receptor (alpha1, alpha2, alpha3, alpha5, beta2, beta3, gamma2S, and gamma2L) and all four subunits of the alpha-amino-3-hydroxy-5-methylsoxazole-4-propionate (AMPA) receptor (GluR1-4) in the hippocampus of 24-month-old rats. All aged hippocampi displayed a remarkable increase (aged/adult ratio, 3.53 +/- 0.54) in the mRNA levels of the short version of the gamma2 subunit in parallel with a similar increase in the gamma2 subunit protein (aged/adult ratio, 2.90 +/- 0.62). However, this increase was not observed in the mature receptor. On the other hand, the expression of the different alpha subunit mRNAs increased moderately with aging, displaying a heterogeneous pattern. The most frequent modification consisted in an increase in the expression of the alpha1 subunit mRNA (aged/adult ratio, 1.26 +/- 0.18), in parallel with a similar increase on the alpha1 protein (aged/adult ratio, 1. 27 +/- 0.12) and in the alpha1 incorporated to the assembled GABA(A) receptor (tested by immunoprecipitation; aged/adult ratio, = 1.20 +/- 0.10). However, in the same hippocampal samples, no major modifications were observed on the expression of the AMPA receptor subunits. As a whole, these results indicated the existence of an increased expression of the GABA(A) receptor subunits and a preservation of the AMPA receptor at the hippocampal formation. These modifications could reflect the existence of specific deficiencies (neuronal loss and/or deafferentiation) on the GABAergic system in the aged rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Cell Membrane / metabolism
  • Chromatography, Affinity
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Hippocampus / metabolism*
  • Isoenzymes / metabolism
  • Precipitin Tests
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / biosynthesis*
  • Receptors, AMPA / chemistry*
  • Receptors, GABA / biosynthesis*
  • Receptors, GABA / chemistry*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA, Complementary
  • Isoenzymes
  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, GABA