Selective Pyramidal Cell Reduction of GABAA Receptor α1 Subunit Messenger RNA Expression in Schizophrenia
Selective Pyramidal Cell Reduction of GABAA Receptor α1 Subunit Messenger RNA Expression in Schizophrenia
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DOI：
10.1038/npp.2011.102
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发表时间：
2011-09-01
影响因子：
7.6
通讯作者：
Lewis, David A.
中科院分区：
文献类型：
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作者：
Glausier, Jill R.;Lewis, David A.
据报道，精神分裂症患者前额皮质 (PFC) 第 3 层的 GABA(A) 受体 α1 亚基（存在于 60% 的皮质 GABA(A) 受体中）的信使 RNA (mRNA) 水平较低。该亚基在锥体细胞和中间神经元中表达，因此每个细胞群中较低的 α1 亚基水平将对净皮质兴奋产生相反的影响。我们使用双标记原位杂交来量化来自匹配的精神分裂症和健康对照受试者的 PFC 第 3 层中包含钙/钙调蛋白依赖性激酶 II α (CaMKII α) 的锥体细胞和包含谷氨酸脱羧酶 65 kDa (GAD65) 的中间神经元中的 GABA(A) α 1 亚基 mRNA 表达。在精神分裂症受试者中，锥体细胞中的平均 GABA(A) α 1 亚基 mRNA 表达显着降低 40%，但中间神经元中的表达没有改变。锥体细胞中较低的α1亚基mRNA表达不能归因于潜在的混杂因素，因此似乎反映了精神分裂症的疾病过程。这些结果表明，精神分裂症患者的锥体细胞抑制减少，而 GABA 神经元的抑制得以维持。这些发现的细胞类型特异性可能反映了面对与这些神经元树突棘密度较低相关的兴奋性驱动减弱时增强第 3 层锥体细胞活性的补偿反应。神经精神药理学 (2011) 36, 2103-2110; doi：10.1038/npp.2011.102； 2011 年 6 月 15 日在线发布
Levels of messenger RNA (mRNA) for the alpha 1 subunit of the GABA(A) receptor, which is present in 60% of cortical GABA(A) receptors, have been reported to be lower in layer 3 of the prefrontal cortex (PFC) in subjects with schizophrenia. This subunit is expressed in both pyramidal cells and interneurons, and thus lower alpha 1 subunit levels in each cell population would have opposite effects on net cortical excitation. We used dual-label in situ hybridization to quantify GABA(A) alpha 1 subunit mRNA expression in calcium/calmodulin-dependent kinase II alpha (CaMKII alpha)-containing pyramidal cells and glutamic acid decarboxylase 65 kDa (GAD65)-containing interneurons in layer 3 of the PFC from matched schizophrenia and healthy comparison subjects. In subjects with schizophrenia, mean GABA(A) alpha 1 subunit mRNA expression was significantly 40% lower in pyramidal cells, but was not altered in interneurons. Lower alpha 1 subunit mRNA expression in pyramidal cells was not attributable to potential confounding factors, and thus appeared to reflect the disease process of schizophrenia. These results suggest that pyramidal cell inhibition is reduced in schizophrenia, whereas inhibition of GABA neurons is maintained. The cell type specificity of these findings may reflect a compensatory response to enhance layer 3 pyramidal cell activity in the face of the diminished excitatory drive associated with the lower dendritic spine density on these neurons. Neuropsychopharmacology (2011) 36, 2103-2110; doi: 10.1038/npp.2011.102; published online 15 June 2011