Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy
Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy
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DOI：
10.1016/j.eplepsyres.2013.01.006
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发表时间：
2013-07-01
影响因子：
2.2
通讯作者：
Ottersen, Ole Petter
中科院分区：
文献类型：
--
作者：
Alvestad, Silje;Hammer, Janniche;Ottersen, Ole Petter
有人提出，硬化海马血管周围终足星形细胞水通道水通道蛋白 4 (AQP4) 的缺失会导致人类内侧颞叶癫痫 (MTLE) 的癫痫发作倾向增加。这种损失是否发生在癫痫发展之前还是癫痫发展的结果仍有待解决。在本研究中，我们研究了 MTLE 红藻氨酸 (KA) 模型中 AQP4 的表达和分布是否在慢性癫痫发作之前（即潜伏期）或发作后（即慢性期）发生改变。免疫金电子显微镜分析显示，KA处理的大鼠已处于潜伏期，足内膜中的AQP4密度降低，而足内膜中的AQP4密度稳定或略有增加。腔内 AQP4 免疫金标记的减少伴随着 AQP4 锚定蛋白 α-肌营养蛋白密度的减少。根据半定量蛋白质印迹分析判断，潜伏期和慢性期与 AQP4 M1 亚型的上调相关。总而言之，该模型的研究结果表明，AQP4 的错误定位（反映星形胶质细胞极化的丧失）是癫痫发生过程中不可或缺的一部分。 (C) 2013 Elsevier B.V. 保留所有权利。
It has been suggested that loss of the astrocytic water channel aquaporin-4 (AQP4) from perivascular endfeet in sclerotic hippocampi contributes to increased seizure propensity in human mesial-temporal lobe epilepsy (MTLE). Whether this loss occurs prior to or as a consequence of epilepsy development remains to be resolved. In the present study, we investigated whether the expression and distribution of AQP4 was altered prior to (i.e., in the latent phase) or after the onset of chronic epileptic seizures (i.e., in the chronic phase) in the kainate (KA) model of MTLE. Immunogold electron microscopic analysis revealed that AQP4 density in adluminal endfoot membranes was reduced in KA treated rats already in the latent phase, while the AQP4 density in the abluminal endfoot membrane was stable or slightly increased. The decrease in adluminal AQP4 immunogold labeling was accompanied by a reduction in the density of AQP4's anchoring protein alpha-syntrophin. The latent and chronic phases were associated with an upregulation of the M1 isoform of AQP4, as judged by semi-quantitative Western blot analysis. Taken together, the findings in this model suggest that a mislocalization of AQP4 - reflecting a loss of astrocyte polarization - is an integral part of the epileptogenic process. (C) 2013 Elsevier B.V. All rights reserved.