Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons
Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons
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DOI：
10.1016/j.schres.2004.05.010
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发表时间：
2005-03-01
影响因子：
4.5
通讯作者：
Harrison, PJ
中科院分区：
文献类型：
--
作者：
Eastwood, SL;Harrison, PJ
精神分裂症患者突触蛋白基因表达改变在海马结构中，可能有特定的海马能神经元及其突触参与，但总体上仍不清楚。在这项原位杂交组织化学（ISHH）研究中，我们研究了四个信息突触蛋白转录：囊泡谷氨酸转运蛋白（VGLUT）1，VGLUT 2，复合蛋白I，和复合蛋白II，在背外侧前额叶皮层（DPFC），上级颞叶皮层（STC），和海马结构，在13例精神分裂症和18名对照。在这些区域，VGLUT 1和复合蛋白II主要由兴奋性神经元表达，而复合蛋白I主要由抑制性神经元表达。精神分裂症患者海马结构和DPFC中VGLUT1 mRNA表达降低，DPFC和STC中复合蛋白II mRNA表达降低，STC中复合蛋白I mRNA表达降低。在精神分裂症组中，海马VGLUT1 mRNA随年龄选择性下降。由于VGLUT2 mRNA水平较低，因此无法定量。这些数据为精神分裂症中的突触病理学提供了额外的证据，即三种突触蛋白基因的表达减少。在海马中，VGLUT1 mRNA的丢失支持表明海马能突触前缺陷突出的数据，而颞叶和额叶皮质中的结果模式表明大致相似的变化可能会影响抑制性和兴奋性神经元。由突触蛋白减少所暗示的突触传递的损害可能有助于表征该病症的皮质神经回路的功能障碍。(C)2004 Elsevier B.V.保留所有权利。
Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder. (C) 2004 Elsevier B.V. All rights reserved.