Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Department of Anatomical Pathology, LabPlus, Auckland City Hospital, Auckland, New Zealand.
Sci Rep. 2021 Nov 2;11(1):21470. doi: 10.1038/s41598-021-00792-8.
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. The GABA signaling system in the brain is comprised of GABA synthesizing enzymes, transporters, GABAA and GABAB receptors (GABAR and GABAR). Alterations in the expression of these signaling components have been observed in several brain regions throughout aging and between sexes in various animal models. The hippocampus is the memory centre of the brain and is impaired in several age-related disorders. It is composed of two main regions: the Cornu Ammonis (CA1-4) and the Dentate Gyrus (DG), which are interconnected with the Entorhinal Cortex (ECx). The age- and sex-specific changes of GABA signaling components in these regions of the human brain have not been examined. This study is the first to determine the effect of age and sex on the expression of GABA signaling components-GABAR α1,2,3,5, β1-3, γ2, GABAR R1 and R2 subunits and the GABA synthesizing enzymes GAD 65/67-in the ECx, and the CA1 and DG regions of the human hippocampus using Western blotting. No significant differences were found in GABAR α1,2,3,5, β1-3, γ2, GABAR R1 and R2 subunit and GAD65/76 expression levels in the ECx, CA1 and DG regions between the younger and older age groups for both sexes. However, we observed a significant negative correlation between age and GABAR α1subunit level in the CA1 region for females; significant negative correlation between age and GABAR β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABAR γ2 subunit expression in the ECx and GABAR R2 subunit expression in the CA1 region. The results indicate that age and sex do not affect the expression of GAD 65/67. In conclusion, our results show age- and sex-related GABAR subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression.
γ-氨基丁酸（GABA）是神经系统中的主要抑制性神经递质。大脑中的 GABA 信号系统由 GABA 合成酶、转运体、GABAA 和 GABAB 受体（GABAR 和 GABAR）组成。在几种动物模型中，随着年龄的增长和性别之间的变化，这些信号成分的表达发生了改变。海马体是大脑的记忆中心，在几种与年龄相关的疾病中受到损害。它由两个主要区域组成：Cornu Ammonis（CA1-4）和齿状回（DG），它们与内嗅皮层（ECx）相互连接。尚未检查这些人类大脑区域中 GABA 信号成分的年龄和性别特异性变化。这项研究首次确定了年龄和性别对 GABA 信号成分-GABAR α1、2、3、5、β1-3、γ2、GABAR R1 和 R2 亚基以及 GABA 合成酶 GAD 65/67 在 ECx 以及人类海马体 CA1 和 DG 区域表达的影响，使用 Western blot 技术。在 ECx、CA1 和 DG 区域中，年轻和年长组的男性和女性之间，GABAR α1、2、3、5、β1-3、γ2、GABAR R1 和 R2 亚基和 GAD65/76 的表达水平没有显着差异。然而，我们观察到女性 CA1 区域中年龄与 GABAR α1 亚基水平之间存在显着负相关；男性 DG 区域中年龄与 GABAR β1、β3 和 γ2 亚基表达之间存在显着负相关。在女性中，在 ECx 中发现年龄与 GABAR γ2 亚基表达之间存在显着正相关，在 CA1 区域中发现年龄与 GABAR R2 亚基表达之间存在显着正相关。结果表明，年龄和性别不影响 GAD 65/67 的表达。总之，我们的结果表明，ECx 和海马体中的 GABAR 亚基与年龄和性别有关，这可能会显着影响 GABA 能神经传递，并构成疾病易感性和进展的基础。
