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

We have investigated the age-dependent modifications in the expression of e ight different subunits of the gamma-aminobutyric acid, type A (GABA(A)) re ceptor (alpha 1, alpha 2, alpha 3, alpha 5, beta 2, beta 3, gamma 2S, and g amma 2L) and all four subunits of the alpha-amino-3-hydroxy-5-methylsoxazol e-4-propionate (AMPA) receptor (GluR1-4) in the hippocampus of 24-month-old rats. All aged hippocampi displayed a remarkable increase (aged/adult rati o, 3.53 +/- 0.54) in the mRNA levels of the short version of the gamma 2 su bunit in parallel with a similar increase in the gamma 2 subunit protein (a ged/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 al pha subunit mRNAs increased moderately with aging, displaying a heterogeneo us pattern. The most frequent modification consisted in an increase in the expression of the alpha 1 subunit mRNA (aged/adult ratio, 1.26 +/- 0.18), i n parallel with a similar increase on the alpha 1 protein (aged/adult ratio , 1.27 +/- 0.12) and in the alpha 1 incorporated to the assembled GABA,rece ptor (tested by immunoprecipitation; aged/adult ratio, = 1.20 +/- 0.10). Ho wever, in the same hippocampal samples, no major modifications were observe d on the expression of the AMPA receptor subunits. As a whole, these result s indicated the existence of an increased expression of the GABA,receptor s ubunits and a preservation of the AMPA receptor at the hippocampal formatio n. These modifications could reflect the existence of specific deficiencies (neuronal loss and/or deafferentiation) on the GABAergic system in the age d rats.