Evidence for a deficit in cholinergic interneurons in the striatum in schizophrenia
Evidence for a deficit in cholinergic interneurons in the striatum in schizophrenia
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DOI：
10.1016/s0306-4522(99)00279-1
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Saper, CB
中科院分区：
文献类型：
--
作者：
Holt, DJ;Herman, MM;Saper, CB
在精神分裂症患者的大脑中已经报道了纹状体的神经化学和功能异常，但是这些变化的细胞基质尚不清楚。我们假设精神分裂症可能涉及纹状体输出的关键调节器之一胆碱能中间神经元的异常。我们测量了精神分裂症患者和对照组大脑纹状体中胆碱能神经元的密度，作为胆碱乙酰转移酶（乙酰胆碱的合成酶）免疫反应性的细胞群标记。作为一个独立的标志物，我们使用的免疫反应钙视网膜蛋白，这是一种蛋白质，这是共定位于几乎所有的胆碱能中间神经元的纹状体胆碱乙酰转移酶。与对照组相比，精神分裂症患者的整个纹状体中胆碱乙酰转移酶阳性和钙视黄蛋白阳性细胞密度显著降低[胆碱乙酰转移酶阳性细胞：对照组：3.21 +/- 0.48个细胞/mm（2）（平均值+/- S.D.），精神分裂症组：2.43 ± 0.68个/mm（2）：，P < 0.02]。这种减少是斑片状的，在腹侧纹状体最为显著（胆碱乙酰转移酶阳性细胞：对照组：3.47 +/- 0.59细胞/mm 2，精神分裂症组：2.52 +/- 0.64细胞/mm 2; P < 0.005），包括腹侧尾状核和中脑核区域。其中3例胆碱能神经元密度最低的精神分裂症患者在1个月至20年内未接受过抗精神病药物治疗，纹状体胆碱能中间神经元数量或功能的减少可能会破坏腹侧纹状体-苍白球-丘脑-前额叶皮质通路的活动，从而导致精神分裂症患者前额叶皮质功能异常。(C)1999年IBRO。出版社：Elsevier Science Ltd
Neurochemical and functional abnormalities of the striatum have been reported in schizophrenic brains, but the cellular substrates of these changes are not known. We hypothesized that schizophrenia may involve an abnormality in one of the key modulators of striatal output, the cholinergic interneuron. We measured the densities of cholinergic neurons in the striatum in schizophrenic and control brains in a blind analysis, using as a marker of this cell population immunoreactivity for choline acetyltransferase, the synthetic enzyme of acetylcholine. As an independent marker, we used immunoreactivity for calretinin, a protein which is co-localized with choline acetyltransferase in virtually all of the cholinergic interneurons of the striatum. A significant decrease in choline acetyltransferase-positive and calretinin-positive cell densities was found in the schizophrenic cases compared with controls in the striatum as a whole [for the choline acetyltransferase-positive cells: controls: 3.21 +/- 0.48 cells/mm(2) (mean +/- S.D.), schizophrenics: 2.43 +/- 0.68 cells/mm(2):, P < 0.02]. The decrease was patchy in nature and most prominent in the ventral striatum (for the choline acetyltransferase-positive cells: controls: 3.47 +/- 0.59 cells/mm2, schizophrenics: 2.52 +/- 0.64 cells/mm(2); P < 0.005) which included the ventral caudate nucleus and nucleus accumbens region. Three of the schizophrenic cases with the lowest densities of cholinergic neurons had not been treated with neuroleptics for periods from more than a month to more than 20 years.A decrease in the number or function of the cholinergic interneurons of the striatum may disrupt activity in the ventral striatal-pallidal-thalamic-prefrontal cortex pathway and thereby contribute to abnormalities in function of the prefrontal cortex in schizophrenia. (C) 1999 IBRO. Published by Elsevier Science Ltd.