Extracellular matrix abnormalities in schizophrenia.
Extracellular matrix abnormalities in schizophrenia.
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DOI：
10.1016/j.neuropharm.2011.08.010
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Berretta, Sabina
中科院分区：
文献类型：
--
作者：
Berretta, Sabina
关键词：
新出现的证据表明脑细胞外基质（ECM）参与精神分裂症（SZ）的病理生理。影响多种ECM成分的异常，包括Reelin和硫酸软骨素蛋白聚糖（CSPGs），已在患有此病的受试者中被描述。有确凿证据支持Reelin的参与，Reelin是一种参与皮质生成、突触功能和谷氨酸NMDA受体调节的ECM糖蛋白，在gaba能神经元的不同群体中普遍表达，并将其分泌到ECM中。在患有SZ和双相情感障碍的受试者中，SZ中Reelin表达的显著变化通常与gaba相关异常有关。我们小组最近的研究结果表明，精神分裂症患者的杏仁核和内嗅皮层中存在影响CSPGs的实质性异常，CSPGs是ECM的主要成分，但双相情感障碍患者没有。神经胶质细胞表达CSPGs的显著增加伴随着神经元周围网络的减少，CSPG和reelin富集的ECM聚集物包裹着不同的神经元群。CSPGs的发育和成体功能，包括神经元迁移、轴突引导、突触和神经传递调节等，与SZ的病理生理高度相关。结合影响其他几个ECM成分的异常报道，这些发现表明ECM是SZ病理的关键组成部分。我们认为，ECM异常可能导致该疾病的几个病理生理方面，包括连通性和神经元迁移中断，突触异常和gaba能、谷氨酸能和多巴胺能神经传递改变。
Emerging evidence points to the involvement of the brain extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Abnormalities affecting several ECM components, including Reelin and chondroitin sulfate proteoglycans (CSPGs), have been described in subjects with this disease. Solid evidence supports the involvement of Reelin, an ECM glycoprotein involved in corticogenesis, synaptic functions and glutamate NMDA receptor regulation, expressed prevalently in distinct populations of GABAergic neurons, which secrete it into the ECM. Marked changes of Reelin expression in SZ have typically been reported in association with GABA-related abnormalities in subjects with SZ and bipolar disorder. Recent findings from our group point to substantial abnormalities affecting CSPGs, a main ECM component, in the amygdala and entorhinal cortex of subjects with schizophrenia, but not bipolar disorder. Striking increases of glial cells expressing CSPGs were accompanied by reductions of perineuronal nets, CSPG- and Reelin-enriched ECM aggregates enveloping distinct neuronal populations. CSPGs developmental and adult functions, including neuronal migration, axon guidance, synaptic and neurotransmission regulation are highly relevant to the pathophysiology of SZ. Together with reports of anomalies affecting several other ECM components, these findings point to the ECM as a key component of the pathology of SZ. We propose that ECM abnormalities may contribute to several aspects of the pathophysiology of this disease, including disrupted connectivity and neuronal migration, synaptic anomalies and altered GABAergic, glutamatergic and dopaminergic neurotransmission.
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DOI：
10.1002/ajmg.b.31093
发表时间：
2010-09-01
影响因子：
2.8
作者：
Ben-David, Eyal;Shifman, Sagiv
通讯作者：
Shifman, Sagiv
影响因子：
--
作者：
Alaerts, Maaike;Ceulemans, Shana;Del-Favero, Jurgen
通讯作者：
Del-Favero, Jurgen
DOI：
10.1073/pnas.0903066106
发表时间：
2009-07-14
影响因子：
11.1
作者：
Benes, Francine M.;Lim, Benjamin;Subburaju, Sivan
通讯作者：
Subburaju, Sivan
影响因子：
3.1
作者：
Akirav I;Maroun M
通讯作者：
Maroun M
影响因子：
--
作者：
Benes, FM
通讯作者：
Benes, FM