Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: An in situ hybridization study
Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: An in situ hybridization study
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DOI：
10.1016/j.biopsych.2005.04.007
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发表时间：
2005-09-01
影响因子：
10.6
通讯作者：
Kleinman, JE
中科院分区：
文献类型：
--
作者：
Holt, DJ;Bachus, SE;Kleinman, JE
背景：纹状体在精神分裂症病理生理学中的作用尚不清楚。在先前的尸检研究中，我们发现精神分裂症患者纹状体中间神经元的胆碱乙酰转移酶（ChAT）染色密度降低。方法：为了确定这一发现是否代表ChAT基因表达的特异性改变，我们使用与人ChAT mRNA互补的寡核苷酸探针原位杂交研究了11名对照和9名精神分裂症受试者的纹状体，前生长抑素原（PPS）mRNA和β-肌动蛋白mRNA。ChAT mRNA阳性神经元的密度，ChAT mRNA表达每神经元，PPS mRNA阳性神经元，和β-actin mRNA的表达水平进行了measurement.Results：有两组之间的PPS mRNA阳性神经元的密度和β-actin mRNA的表达水平在整个条纹，或在ChAT mRNA阳性神经元的密度在尾状核或壳核没有显着差异。然而，在腹侧纹状体中，ChAT mRNA阳性神经元的平均密度降低到对照水平的26% in the schizophrenic group.Conclusions：有一个减少的数量或功能的腹侧纹状体的胆碱能中间神经元在精神分裂症。
Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia.Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and beta-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and beta-actin mRNA expression levels were measured.Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of beta-actin mRNA expression throughout the striation, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group.Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.