GABA(A) receptor subunit expression changes in the rat cerebellum and cerebral cortex during aging

Significant aging-related decreased expression of various GABA(A)R subunit mRNAs (α₁, γ₂, β₂, β₃ and δ) was found in both cerebellum and cerebral cortex using quantitative dot blot and in situ hybridization techniques. Contrary to the other subunits, the α₆ mRNA expression was significantly increased in the aged cerebellum. Parallel age-related changes in protein expression for γ₂ and β(2/3) (decrease) and α₆ (increase) were revealed in cerebellum by quantitative immunocytochemistry. However, no significant changes in α₁ protein expression nor in the number or affinity of [³H]zolpidem binding sites were detected in cerebellum even though α₁ mRNA expression was significantly decreased in the aged rat. Age-related increased expression of α₆ mRNA and protein in the cerebellum was accompanied by no significant changes in the number of diazepam-insensitive [³H]Ro15-4513 binding sites. In the cerebral cortex, no changes in the protein expression of the main GABA(A) receptor subunits (α₁, γ₂ and β(2/3)) were observed which contrasted with the age-related decreased expression of the corresponding mRNAs. No significant changes in the number or affinity of [³H]zolpidem binding sites were observed in the cerebral cortex. Thus, age-related changes in the mRNA expression of a particular subunit does not necessarily lead to similar changes in protein or assembly into mature GABA(A) receptors. The results reveal the existence of complex regulatory mechanisms of GABA(A) receptor expression, at the transcriptional, translational and post-translational and/or assembly levels, which vary with the subunit and brain area.