DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex

被引:85
作者
Kirkpatrick, Brian
Xu, Leyan
Cascella, Nicola
Ozeki, Yuji
Sawa, Akira
Roberts, Rosalinda C.
机构
[1] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA
[2] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21205 USA
关键词
development; schizophrenia; synapses; postmortem; plasticity;
D O I
10.1002/cne.21007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:436 / 450
页数:15
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