Pantazopoulos Harry, Woo Tsung-Ung W, Lim Maribel P, Lange Nicholas, Berretta Sabina
Translational Neuroscience Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Arch Gen Psychiatry. 2010 Feb;67(2):155-66. doi: 10.1001/archgenpsychiatry.2009.196.
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 parvalbumin-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.
硫酸软骨素蛋白聚糖（CSPGs）是脑细胞外基质的主要成分，可调节与精神分裂症发病机制高度相关的发育和成年期神经功能。这些功能，以及正常人类杏仁核内星形胶质细胞中CSPGs的显著表达，以及该疾病中星形胶质细胞功能破坏的证据，表明CSPG-胶质细胞相互作用参与了精神分裂症的发病过程。
硫酸软骨素蛋白聚糖相关异常涉及精神分裂症患者杏仁核和内嗅皮质中的胶质细胞和细胞外基质细胞周聚集体（神经元周围网）。
尸检病例对照研究。
哈佛医学院麦克莱恩医院转化神经科学实验室。标本取自麦克莱恩医院的哈佛脑组织资源中心。
两组独立的健康对照者（n = 15；n = 10）和精神分裂症患者（n = 11；n = 10），以及一组双相情感障碍患者（n = 11）。
定量、免疫细胞化学和组织学尸检研究。
杏仁核深部核团和内嗅皮质中CSPG阳性胶质细胞和神经元周围网的数值密度、胶质纤维酸性蛋白阳性星形胶质细胞以及小白蛋白阳性神经元的总数。
在精神分裂症患者中，杏仁核深部核团（419%-1162%）和内嗅皮质（第二层；480%-1560%）中检测到CSPG阳性胶质细胞大量增加。杏仁核外侧核和外侧内嗅皮质（第二层）的神经元周围网减少。胶质纤维酸性蛋白阳性胶质细胞的数值密度和小白蛋白阳性神经元的总数未改变。双相情感障碍患者中CSPG阳性成分的变化可忽略不计。
精神分裂症中功能相关分子的显著变化表明细胞外基质-胶质细胞相互作用在该疾病发病机制中起关键作用。迄今为止未被怀疑的这些相互作用的破坏，可能是导致精神分裂症中神经元迁移、突触连接以及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异常表明精神分裂症在关键颞叶内侧区域病理生理学的一个独特方面。
