Regulation of brain water: is there a role for aquaporins in epilepsy?
Regulation of brain water: is there a role for aquaporins in epilepsy?
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DOI：
10.1111/j.1535-7511.2005.05310.x
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发表时间：
2005-05-01
影响因子：
3.6
通讯作者：
Rogawski, Michael A
中科院分区：
文献类型：
--
作者：
Dudek, F Edward;Rogawski, Michael A
李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军。[08:493 - 502]内侧颞叶癫痫患者的海马体经常硬化和萎缩，这种情况被称为硬化症。MRI显示t2加权信号增加，而弥散加权成像显示硬化海马的表观弥散系数较高，表明含水量增加。由于水运输似乎与K+清除和神经元兴奋性相耦合，因此我们探索了硬化海马中水稳态紊乱的分子基础。采用实时定量聚合酶链式反应、光镜免疫组织化学和高分辨率免疫金标记技术研究脑内主要水通道水通道蛋白AQP-4的表达。在医学上难治性颞叶癫痫患者的硬化海马中观察到AQP-4的显著增加，而在非硬化海马中则没有。这种增加与星形胶质细胞标志物胶质原纤维酸性蛋白的增加呈正相关。AQP-4定位于星形胶质细胞的质膜，包括血管周围终足。采用Affymetrix GeneChip U133A高通量基因表达分析评估与AQP-4升高相关的基因表达，并采用Ingenuity Pathways analysis研究相关基因网络。AQP-4的表达与肌营养不良蛋白基因的表达减少有关，该基因与AQP-4在血管周围终足的锚定有关。肌营养不良蛋白的表达减少可能表明AQP-4在星形胶质细胞中的分布极性丧失。我们得出结论，AQP-4和肌营养不良蛋白的表达紊乱可能是硬化海马中离子和水稳态丧失的一个潜在因素，并假设报道的这些变化可能有助于硬化组织的致痫特性。
Aquaporin-4 Is Increased in the Sclerotic Hippocampus in Human Temporal Lobe EpilepsyLee TS, Eid T, Mane S, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NCActa Neuropathol (Berl) 2004;108:493–502The hippocampus of patients with mesial temporal lobe epilepsy is often hardened and shrunken, a condition known as sclerosis. MRI reveals an increase in the T2-weighted signal, whereas diffusion-weighted imaging shows a higher apparent diffusion coefficient in sclerotic hippocampi, indicating increased water content. As water transport appears to be coupled to K+clearance and neuronal excitability, the molecular basis of the perturbed water homeostasis in the sclerotic hippocampus was explored. The expression of aquaporin-4 (AQP-4), the predominant water channel in the brain, was studied with quantitative real-time polymerase chain reaction analysis, light-microscopic immunohistochemistry, and high-resolution immunogold labeling. A significant increase in AQP-4 was observed in sclerotic, but not in nonsclerotic, hippocampi obtained from patients with medically intractable temporal lobe epilepsy. This increase was positively correlated with an increase in the astrocyte marker glial fibrillary acidic protein. AQP-4 was localized to the plasma membranes of astrocytes including the perivascular endfeet. Gene expression associated with increased AQP-4 was evaluated by high-throughput gene-expression analysis with Affymetrix GeneChip U133A, and related gene networks were investigated with Ingenuity Pathways Analysis. AQP-4 expression was associated with a decrease in expression of the dystrophin gene, a protein implicated in the anchoring of AQP-4 in perivascular endfeet. The decreased expression of dystrophin may indicate a loss of polarity in the distribution of AQP-4 in astrocytes. We conclude that the perturbed expression of AQP-4 and dystrophin may be one factor underlying the loss of ion and water homeostasis in the sclerotic hippocampus and hypothesize that the reported changes may contribute to the epileptogenic properties of the sclerotic tissue.