GABAa and a-Amino-3-hydroxy-5-methylsoxazole-4-propionate receptors are differentially affected by aging in the rat hippocampus

Abstract

We have investigated the age-dependent modifications in the expression of eight different subunits of the γ-aminobutyric acid, type A (GABAA) receptor (α1, α2, α3, α5, β2, β3, γ2S, and γ2L) and all four subunits of the α-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 γ2 subunit in parallel with a similar increase in the γ2 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 α subunit mRNAs increased moderately with aging, displaying a heterogeneous pattern. The most frequent modification consisted in an increase in the expression of the α1 subunit mRNA (aged/adult ratio, 1.26 ± 0.18), in parallel with a similar increase on the α1 protein (aged/adult ratio, 1.27 ± 0.12) and in the α1 incorporated to the assembled GABAA 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 GABAA 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 rat