Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures
Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures
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癫痫发作后梨状皮层酸敏感离子通道亚型的表达模式改变
DOI：
10.1007/s12035-015-9130-5
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
刘备
中科院分区：
文献类型：
--
作者：
刘备
梨状皮质（PC）是高度敏感的化学和电癫痫发作诱导。癫痫样活动与细胞外pH的酸转移有关，这表明PC神经元表达的酸敏感离子通道（ASIC）可能有助于这种增强的致癫痫电位。在癫痫大鼠和内侧颞叶癫痫（TLE）患者的手术样本中，PC第II层ASIC 1a免疫阳性神经元出现肿胀，树突状延长，第III层ASIC 1a阳性神经元丢失，这与TLE诱导的可塑性和细胞死亡的脆弱性增强一致。在大鼠中，匹鲁卡品诱导的癫痫发作导致短暂的下调ASIC 1a和随之而来的上调ASIC 2a在癫痫发作后的头几天。这些表达变化可能是由于癫痫发作诱导的氧化应激引起的，与ASIC 1a类似的相互变化，并且在施加H2 O2后在PC 12细胞中观察到ASIC 2a表达。ASIC 1a/ASIC 2a异聚体的比例在癫痫持续状态（SE）后的急性期减少，但在大鼠自发性癫痫发作的潜伏期增加。通过RNAi敲低ASIC 2a降低了原代神经元中的树突长度和棘密度，表明在大鼠中，姜黄素诱导的ASIC 2a上调有助于PC层II中的树突延长。在匹鲁卡品之前给予ASIC抑制剂阿米洛利降低了大鼠达到拉辛IV级癫痫发作的比例，保护了第II层和第III层神经元，并延长了SE后急性期的生存期。我们的研究结果表明，ASIC可能会增加PC癫痫发生的易感性。抑制ASIC，特别是ASIC 2a，可以抑制源自PC的癫痫发作。
The piriform cortex (PC) is highly susceptible to chemical and electrical seizure induction. Epileptiform activity is associated with an acid shift in extracellular pH, suggesting that acid-sensing ion channels (ASICs) expressed by PC neurons may contribute to this enhanced epileptogenic potential. In epileptic rats and surgical samples from patients with medial temporal lobe epilepsy (TLE), PC layer II ASIC1a-immunopositive neurons appeared swollen with dendritic elongation, and there was loss of ASIC1a-positive neurons in layer III, consistent with enhanced vulnerability to TLE-induced plasticity and cell death. In rats, pilocarpine-induced seizures led to transient downregulation of ASIC1a and concomitant upregulation of ASIC2a in the first few days post-seizure. These changes in expression may be due to seizure-induced oxidative stress as a similar reciprocal change in ASIC1a, and ASIC2a expression was observed in PC12 cells following H2O2application. The proportion of ASIC1a/ASIC2a heteromers was reduced in the acute phase following status epilepticus (SE) but increased during the latent phase when rats developed spontaneous seizures. Knockdown of ASIC2a by RNAi reduced dendritic length and spine density in primary neurons, suggesting that seizure-induced upregulation of ASIC2a contributes to dendritic lengthening in PC layer II in rats. Administration of the ASIC inhibitor amiloride before pilocarpine reduced the proportion of rats reaching Racine level IV seizures, protected layer II and III neurons, and prolonged survival in the acute phase following SE. Our findings suggest that ASICs may enhance susceptibility to epileptogenesis in the PC. Inhibition of ASICs, particularly ASIC2a, may suppress seizures originating in the PC.
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影响因子：
5.5
作者：
de la Rosa, DA;Krueger, SR;Canessa, CM
通讯作者：
Canessa, CM
影响因子：
3.3
作者：
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影响因子：
16.2
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影响因子：
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作者：
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影响因子：
2
作者：
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通讯作者：
A. Ekholm;T. Kristian;B. Siesjö