Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia.
Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia.
复制标题
被诊断为精神分裂症的受试者的杏仁核和内嗅皮层的细胞外基质异常。
DOI：
10.1001/archgenpsychiatry.2009.196
复制
发表时间：
2010-02
影响因子：
--
通讯作者：
Berretta, Sabina
中科院分区：
文献类型：
--
作者：
Pantazopoulos, Harry;Woo, Tsung-Ung W.;Lim, Maribel P.;Lange, Nicholas;Berretta, Sabina
硫酸软骨素蛋白多糖（CSPGs）是脑细胞外基质的主要成分，其调节发育和成人神经功能，与精神分裂症的发病机制高度相关。这些功能，加上正常人类杏仁核内星形胶质细胞中CSPGs的显著表达，以及这种疾病中星形胶质细胞功能破坏的证据，表明精神分裂症中涉及cspg -胶质相互作用。硫酸软骨素蛋白聚糖相关异常涉及杏仁核和内鼻皮层的神经胶质细胞和细胞外基质细胞周围聚集体（神经元周围网）。死后病例对照研究。哈佛医学院麦克莱恩医院的转化神经科学实验室。样本来自麦克林医院的哈佛脑组织资源中心。两个独立的队列：健康对照（n= 15; n= 10）和精神分裂症（n=11; n= 10）受试者和双相情感障碍（n=11）受试者。定量，免疫细胞学和组织学死后调查。杏仁核深部核和嗅内皮层cspg阳性的胶质细胞和神经元周围网、胶质纤维酸性蛋白阳性的星形胶质细胞的数值密度和小蛋白阳性的神经元总数。在精神分裂症中，在杏仁核深部核（419%-1162%）和内嗅皮层（第二层；480%-1560%）检测到cspg阳性胶质细胞大量增加。杏仁核外侧核和外侧鼻内皮层（第二层）的神经网络减少。胶质原纤维酸性蛋白阳性胶质细胞的数值密度和小蛋白阳性神经元的总数不变。在双相情感障碍患者中，cspg阳性因子的变化可以忽略不计。精神分裂症中功能相关分子的显著变化表明细胞外基质-神经胶质相互作用在这种疾病的发病机制中起着关键作用。这些相互作用的破坏，迄今未被怀疑，可能是导致精神分裂症中神经元迁移、突触连通性以及gaba能、谷氨酸能和多巴胺能神经传递紊乱的一个统一因素。双相情感障碍中缺乏CSPG异常指出了精神分裂症在关键内侧颞叶区域的病理生理学的一个独特方面。
Chondroitin sulfate proteoglycans (CSPGs), a main component of the brain extracellular matrix, regulate developmental and adult neural functions that are highly relevant to the pathogenesis of schizophrenia. Such functions, together with marked expression of CSPGs in astrocytes within the normal human amygdala and evidence of a disruption of astrocytic functions in this disease, point to involvement of CSPG-glial interactions in schizophrenia. Chondroitin sulfate proteoglycan–related abnormalities involve glial cells and extracellular matrix pericellular aggregates (perineuronal nets) in the amygdala and entorhinal cortex of subjects with schizophrenia. Postmortem case-control study. The Translational Neuroscience Laboratory at McLean Hospital, Harvard Medical School. Specimens were obtained from the Harvard Brain Tissue Resource Center at McLean Hospital. Two separate cohorts of healthy control (n = 15; n = 10) and schizophrenic (n = 11; n = 10) subjects and a cohort of subjects with bipolar disorder (n=11). Quantitative, immunocytological, and histological postmortem investigations. Numerical densities of CSPG-positive glial cells and perineuronal nets, glial fibrillary acidic protein-positive astrocytes, and total numbers of parvalbumin-positive neurons in the deep amygdala nuclei and entorhinal cortex. In schizophrenia, massive increases in CSPG-positive glial cells were detected in the deep amygdala nuclei (419%–1162%) and entorhinal cortex (layer II; 480%–1560%). Perineuronal nets were reduced in the lateral nucleus of the amygdala and lateral entorhinal cortex (layer II). Numerical densities of glial fibrillary acidic protein-positive glial cells and total numbers of parval-bumin-positive neurons were unaltered. Changes in CSPG-positive elements were negligible in subjects with bipolar disorder. Marked changes in functionally relevant molecules in schizophrenia point to a pivotal role for extracellular matrix–glial interactions in the pathogenesis of this disease. Disruption of these interactions, unsuspected thus far, may represent a unifying factor contributing to disturbances of neuronal migration, synaptic connectivity, and GABAergic, glutamatergic, and dopaminergic neurotransmission in schizophrenia. The lack of CSPG abnormalities in bipolar disorder points to a distinctive aspect of the pathophysiology of schizophrenia in key medial temporal lobe regions.
登录
查看更多内容
DOI：
10.1023/a:1025751900356
发表时间：
2002-07-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Butt, AM;Kiff, J;Berry, M
通讯作者：
Berry, M
影响因子：
11
作者：
Buxbaum, J. D.;Georgieva, L.;O'Donovan, M. C.
通讯作者：
O'Donovan, M. C.
影响因子：
3
作者：
Dityatev, Alexander;Brueckner, Gert;Schachner, Melitta
通讯作者：
Schachner, Melitta
影响因子：
15.9
作者：
Celio, MR;Spreafico, R;Vitellaro-Zuccarello, L
通讯作者：
Vitellaro-Zuccarello, L
DOI：
10.1016/s0165-3806(98)00088-1
发表时间：
1998-08-08
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Charvet, I;Hemming, FJ;Saxod, R
通讯作者：
Saxod, R