DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex
DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex
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DOI：
10.1002/cne.21007
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发表时间：
2006-07-20
影响因子：
2.5
通讯作者：
Roberts, Rosalinda C.
中科院分区：
文献类型：
--
作者：
Kirkpatrick, Brian;Xu, Leyan;Roberts, Rosalinda C.
DISC 1是跨越与精神分裂症风险增加相关的易位的1号染色体断点的两个基因之一。DISC 1已在多种哺乳动物的脑中被鉴定，但以前没有在人类新皮质中进行过免疫细胞化学研究。我们研究了正常人脑额叶和顶叶皮层（BA 4，9，39和46）的DISC 1免疫反应。在光学显微镜水平，免疫标记在神经元、多个细胞群体和白色物质中突出。在超微结构水平上，与突触功能相关的结构中染色显著。免疫标记的轴突终末占所有终末的8%，形成不对称和对称突触。标记的轴突终末与标记的棘和树突形成突触;在某些情况下，仅标记突触后结构的突触后密度（PSD）。然而，最常见的配置是一个未标记的轴突终末形成一个不对称的突触与脊柱，沉积在PSD和整个脊柱的免疫反应。DISC 1在多种类型的突触中的存在表明DISC 1参与皮质和丘脑皮质的连接。染色也存在于核糖体，染色质的一部分，在树突状轴，和一些微管。标记是缺席的高尔基体和多泡体，这是与蛋白质排泄。这些解剖学定位数据表明DISC 1参与突触活动和微管功能，并且与其成年功能的有限数据一致。
Disrupted-In-Schizophrenia 1 (DISC1) is one of two genes that straddle the chromosome 1 breakpoint of a translocation associated with an increased risk of schizophrenia. DISC 1 has been identified in the brain of various mammalian species, but no previous immunocytochemical studies have been conducted in human neocortex. We examined DISC1 immunoreactivity in frontal and parietal cortex (BA 4, 9, 39, and 46) in normal human brain. At the light microscopic level, immunolabeling was prominent in the neuropil, in multiple populations of cells, and in the white matter. At the ultrastructural level, staining was prominent in structures associated with synaptic function. Immunolabeled axon terminals comprised 8% of all terminals and formed both asymmetric and symmetric synapses. Labeled axon terminals formed synapses with labeled spines and dendrites; in some, only the postsynaptic density (PSD) of the postsynaptic structure was labeled. The most common configuration, however, was an unlabeled axon terminal forming an asymmetric synapse with a spine that had immunoreactivity deposited on the PSD and throughout the spine. The presence of DISC1 in multiple types of synapses suggests the involvement of DISC 1 in corticocortical as well as thalamocortical connections. Staining was also present in ribosomes, parts of the chromatin, in dendritic shafts, and on some microtubules. Labeling was absent from the Golgi apparatus and multivesicular bodies, which are associated with protein excretion. These anatomical localization data suggest that DISC1 participates in synaptic activity and microtubule function, and are consistent with the limited data on its adult function.