Remodeling of extracellular matrix and epileptogenesis
Remodeling of extracellular matrix and epileptogenesis
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DOI：
10.1111/j.1528-1167.2010.02612.x
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发表时间：
2010-01-01
期刊：
影响因子：
5.6
通讯作者：
Dityatev, Alexander
中科院分区：
文献类型：
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作者：
Dityatev, Alexander
脑细胞外基质（ECM）是由神经元和神经胶质细胞合成和分泌的分子组成，在细胞外空间形成稳定的多种成分的聚集体。在成熟的大脑中，ECM经历缓慢的周转和抑制结构可塑性，同时支持多种生理过程，包括体周γ-氨基丁酸（GABA）能抑制，突触可塑性和稳态调节。癫痫发作导致ECM的显著重塑，其可能本质上参与癫痫发生的不同方面。这一观点得到了人类遗传学研究的支持，ECM分子和癫痫的联系，数据显示在缺乏ECM分子的小鼠癫痫发生改变，并有证据表明，ECM可能会形成苔藓纤维，颗粒细胞分散和星形胶质细胞增生的胚胎诱导发芽。因此，抑制癫痫引起的ECM重塑或抑制重塑的ECM触发的信号传导可能提供有效的治疗策略来对抗癫痫发生的进展。
P>Extracellular matrix (ECM) in the brain is composed of molecules synthesized and secreted by neurons and glial cells, which form stable aggregates of diverse composition in the extracellular space. In the mature brain, ECM undergoes a slow turnover and restrains structural plasticity while supporting multiple physiologic processes, including perisomatic gamma-aminobutyric acid (GABA)ergic inhibition, synaptic plasticity, and homeostatic regulations. Seizures lead to striking remodeling of ECM, which may be essentially engaged in different aspects of epileptogenesis. This view is supported by human genetic studies linking ECM molecules and epilepsy, by data showing altered epileptogenesis in mice deficient in ECM molecules, and by evidence that ECM may shape seizure-induced sprouting of mossy fibers, granule cell dispersion, and astrogliosis. Therefore, restraining seizure-induced remodeling of ECM or suppressing the signaling triggered by the remodeled ECM might provide effective therapeutic strategies to antagonize the progression of epileptogenesis.