Pathological alterations of chondroitin sulfate moiety in postmortem hippocampus of patients with schizophrenia
Pathological alterations of chondroitin sulfate moiety in postmortem hippocampus of patients with schizophrenia
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DOI：
10.1016/j.psychres.2018.10.062
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发表时间：
2018-12
影响因子：
11.3
通讯作者：
Takayuki Yukawa;Y. Iwakura;N. Takei;M. Saito;Yuichiro Watanabe;K. Toyooka;M. Igarashi;K. Niizato;Kenichi Oshima;Yasuto Kunii;H. Yabe;Junya Matsumoto;Akira Wada;Mizuki Hino;S. Iritani;S. Niwa;R. Takeuchi;H. Takahashi;A. Kakita;T. Someya;H. Nawa
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文献类型：
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作者：
Takayuki Yukawa;Y. Iwakura;N. Takei;M. Saito;Yuichiro Watanabe;K. Toyooka;M. Igarashi;K. Niizato;Kenichi Oshima;Yasuto Kunii;H. Yabe;Junya Matsumoto;Akira Wada;Mizuki Hino;S. Iritani;S. Niwa;R. Takeuchi;H. Takahashi;A. Kakita;T. Someya;H. Nawa
神经周围网包含硫酸软骨素部分及其核心蛋白，其神经病理学改变与精神分裂症有关。为了探讨精神分裂症神经周围网损伤的分子机制，我们测量了精神分裂症患者和对照受试者三个脑区（死后背外侧前额叶皮层、尾状核和海马）硫酸软骨素部分（神经周围网的主要成分）的免疫反应性。 4-硫酸软骨素和 6-硫酸软骨素部分的免疫印迹显示患者海马中 180kD 软骨素 4-硫酸盐免疫反应带的强度显着增加，尽管我们检测到其与任何其他分子大小或其他大脑区域的免疫反应性没有显着变化。免疫反应性水平与死后间隔、年龄或储存时间无关。我们未能发现长期接受氟哌啶醇治疗的大鼠海马中 4-硫酸软骨素免疫反应性分子范围相似的增加。这些结果表明，4-硫酸软骨素部分的水平变化可能导致精神分裂症患者的神经周围网络异常。
Perineuronal nets comprise chondroitin sulfate moieties and their core proteins, and their neuropathological alterations have been implicated in schizophrenia. To explore the molecular mechanism of the perineuronal net impairments in schizophrenia, we measured the immunoreactivity of chondroitin sulfate moieties, major components of perineuronal nets, in three brain regions (postmortem dorsolateral prefrontal cortex, caudate nucleus, and hippocampus) of schizophrenia patients and control subjects. Immunoblotting for chondroitin 4-sulfate and chondroitin 6-sulfate moieties revealed a significant increase in intensity of a 180 kD band of chondroitin 4-sulfate immunoreactivity in the hippocampus of patients, although we detected no significant alteration in their immunoreactivities with any other molecular sizes or in other brain regions. The levels of immunoreactivity were not correlated with postmortem interval, age, or storage time. We failed to find such an increase in a similar molecular range of the chondroitin 4-sulfate immunoreactivity in the hippocampus of the rats chronically treated with haloperidol. These results suggest that the level alteration of the chondroitin 4-sulfate moiety might contribute to the perineuronal net abnormality found in patients with schizophrenia.