AGE-RELATED DECREASE OF GABA(A) RECEPTOR SUBUNITS AND GLUTAMIC-ACID DECARBOXYLASE IN THE RAT INFERIOR COLLICULUS

A selective age-related decrease in both the protein and mRNA levels of the most abundant GABA(A) receptor subunits has been revealed in the rat inferior colliculus. The number (not affinity) of the native and fully assembled GABA(A) receptors assayed by H-3-muscimol binding was also decreased (35-49%). The decrease in GABA receptors was accompanied by a decrease in the protein and mRNA of the GABA-synthesizing enzyme glutamic acid decarboxylase. No other region of the rat brain showed such large age-related changes in these GABAergic synaptic molecules. Specific antibodies and riboprobes in conjunction with a computerized image analysis system were used to quantify immunocytochemistry and in situ hybridization. In old Sprague-Dawley rats, the combination of beta(2) and beta(3) peptide subunits was reduced 55%, while the beta(2) and beta(3) mRNAs were decreased 31% and 22%, respectively. The gamma(2S) and gamma(2L) subunit proteins decreased 43% and 21%, respectively, while the gamma(2) mRNA, including both short and long forms, was reduced 61%. The alpha(1) subunit protein was decreased 28%, whereas the alpha(1) mRNA decreased 40%. The glutamic acid decarboxylase protein was reduced 62% while GAD(65) mRNA decreased 42%. Similar age-related changes were also observed in the inferior colliculus of Fischer-344 rats. In contrast, no changes were observed in the level of expression of some glial and/or neuronal proteins such as S-100, glial fibrillary acidic protein, and 160 KDa neurofilament protein in the inferior colliculus. These results demonstrate the existence of an age-related decline of GABAergic neurotransmission in the rat inferior colliculus that might contribute to some age-related neural auditory dysfunctions.