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 o f 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 accompanie d by a decrease in the protein and mRNA of the GABA-synthesizing enzym e 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 i n situ hybridization. In old Sprague-Dawley rats, the combination of b eta(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%, respectivel y, while the gamma(2) mRNA, including both short and long forms, was r educed 61%. The alpha(1) subunit protein was decreased 28%, whereas th e 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 fibrillar y acidic protein, and 160 KDa neurofilament protein in the inferior co lliculus. These results demonstrate the existence of an age-related de cline of GABAergic neurotransmission in the rat inferior colliculus th at might contribute to some age-related neural auditory dysfunctions.