Age-related alterations in GABA_A receptor subunits in the nonhuman primate hippocampus

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• 作者：Robert A. Rissman ; Romy Nocera ; Laura M. Fuller ; Jeffrey H. Kordower and David M. Armstrong
• 关键词：GABA receptor subunit ; Benzodiazepine ; Hippocampus ; Aging ; Densitometry ; Nonhuman primate ; Immunohistochemistry
• 刊名：Brain Research
• 出版年：2006
• 出版时间：16 February 2006
• 年：2006
• 卷：1073-1074
• 期：Complete
• 页码：120-130
• 全文大小：819 K

文摘

Pharmacological studies have documented that altered drug responses, particularly to benzodiazepines, are common in elderly populations. While numerous factors may contribute to changes in drug response, age-related alterations in the molecular composition of GABA_A receptors may be a key factor in regulating these responses. We employed quantitative densitometry to examine the cytological features and density of highly prevalent hippocampal GABA_A receptor subunits (α1 and β2/3) in young and aged rhesus monkeys. α1 and β2/3 subunit immunostaining was differentially distributed throughout the hippocampus. In addition, β2/3 immunolabeling in aged monkeys was characterized by marked intersubject variability in labeling intensity, with dramatic reductions present in 3 of 5 samples. α1 immunolabeling in aged monkeys was significantly reduced in the CA2 and CA3 subregions, and in hilus/polymorphic layer of the dentate gyrus. Collectively, our findings demonstrate that not only are GABA_A receptor subunits differentially distributed throughout the hippocampus, but they are also differentially altered with increased age—changes that may have an important impact on the binding properties of GABA_A receptor pharmacological agents.