GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus
GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus
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DOI：
10.1111/jnc.14325
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发表时间：
2018-06-01
影响因子：
4.7
通讯作者：
Faull, Richard L.
中科院分区：
文献类型：
--
作者：
Kwakowsky, Andrea;Guzman, Beatriz Calvo-Flores;Faull, Richard L.
γ -氨基丁酸（GABA）是中枢神经系统的主要抑制性神经递质。GABA A型受体（GABA(A)Rs）在阿尔茨海默病（AD）中受到严重影响。然而，GABA(A)Rs在AD脑中的分布和亚基组成尚不清楚。这是首次全面研究显示GABA(A)R亚基1- 3,5,1-3和2在人类AD海马、内鼻皮层和颞上回中表达的脑区域和细胞层特异性改变。在晚期AD组织样本中，我们发现除了3和1亚基保存完好外，所有研究的GABA(A)Rs亚基都发生了显著变化。最显著的变化包括与AD相关的GABA(A) r1在CA3区各层、齿状回颗粒层和门部的表达增加。我们发现，在AD病例中，GABA(a) r2在CA1-3的stri . orium和CA2,3的stri . radiatum中表达显著增加，而在CA1区的stri . pyramidale中表达显著减少。在AD中，GABA(a) r5亚基在CA1区锥体区、东侧区表达显著增加，在颞上回表达显著降低。我们还发现，在齿状回的CA2、str颗粒和str分子中，GABA(a)R 3亚基免疫反应性显著降低。综上所述，这些研究结果表明，GABA(A)R亚基的表达在AD中显示出脑区域和层特异性的改变，这些变化可能显著影响和改变GABA(A)R在疾病中的功能。
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA type A receptors (GABA(A)Rs) are severely affected in Alzheimer's disease (AD). However, the distribution and subunit composition of GABA(A)Rs in the AD brain are not well understood. This is the first comprehensive study to show brain region- and cell layer-specific alterations in the expression of the GABA(A)R subunits 1-3, 5, 1-3 and 2 in the human AD hippocampus, entorhinal cortex and superior temporal gyrus. In late-stage AD tissue samples using immunohistochemistry we found significant alteration of all investigated GABA(A)Rs subunits except for 3 and 1 that were well preserved. The most prominent changes include an increase in GABA(A)R 1 expression associated with AD in all layers of the CA3 region, in the stratum (str.) granulare and hilus of the dentate gyrus. We found a significant increase in GABA(A)R 2 expression in the str. oriens of the CA1-3, str. radiatum of the CA2,3 and decrease in the str. pyramidale of the CA1 region in AD cases. In AD there was a significant increase in GABA(A)R 5 subunit expression in str. pyramidale, str. oriens of the CA1 region and decrease in the superior temporal gyrus. We also found a significant decrease in the GABA(A)R 3 subunit immunoreactivity in the str. oriens of the CA2, str. granulare and str. moleculare of the dentate gyrus. In conclusion, these findings indicate that the expression of the GABA(A)R subunits shows brain region- and layer-specific alterations in AD, and these changes could significantly influence and alter GABA(A)R function in the disease.