GABA sub(A) and alpha -Amino-3-hydroxy-5-methylsoxazole-4-propionate Receptors Are Differentially Affected by Aging in the Rat Hippocampus

• Published in: The Journal of biological chemistry 2000-06, Vol.275 (26), p.19585-19593
• Main Authors: Ruano, D, Araujo, F, Revilla, E, Vela, J, Bergis, O, Vitorica, J
• Format: Article
• Language: English
• ISSN: 0021-9258

We have investigated the age-dependent modifications in the expression of eight different subunits of the gamma -aminobutyric acid, type A (GABA sub(A)) receptor ( alpha 1, alpha 2, alpha 3, alpha 5, beta 2, beta 3, gamma 2S, and gamma 2L) 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 plus or minus 0.54) in the mRNA levels of the short version of the gamma 2 subunit in parallel with a similar increase in the gamma 2 subunit protein (aged/adult ratio, 2.90 plus or minus 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 alpha 1 subunit mRNA (aged/adult ratio, 1.26 plus or minus 0.18), in parallel with a similar increase on the alpha 1 protein (aged/adult ratio, 1.27 plus or minus 0.12) and in the alpha 1 incorporated to the assembled GABA sub(A) receptor (tested by immunoprecipitation; aged/adult ratio, = 1.20 plus or minus 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 sub(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.