Inverse relationship between seizure expression and extrasynaptic NMDAR function following chronic NMDAR inhibition.
Inverse relationship between seizure expression and extrasynaptic NMDAR function following chronic NMDAR inhibition.
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DOI：
10.1111/j.1528-1167.2010.02621.x
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发表时间：
2010-07
期刊：
影响因子：
5.6
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Bausch SB;He S;Dong Y
我们之前的研究表明，在用nr2b选择性拮抗剂Ro25,6981进行慢性治疗后，器官型海马切片培养中涉及齿状颗粒细胞的电图癫痫发作显著减少，但在用高亲和力竞争拮抗剂APV进行慢性治疗后，电图癫痫发作增加。为了开始研究NMDAR拮抗剂对癫痫发作的不同作用的潜在机制，我们在海马片培养的齿状颗粒细胞中进行了电生理实验，这些细胞在整个17-21天的培养期内分别用载药、Ro25、6981或D-APV处理。最初的实验显示mEPSC测量与癫痫发作之间缺乏关联，这表明mEPSC的变化不太可能解释D-APV和ro25,6981对癫痫发作的不同影响。然而，在长期使用D-APV的培养物中，nmdar介导的强直性电流的振幅降低，而在长期使用Ro25、6981的培养物中则显著增强。由于强直性NMDAR电流主要由突触外NMDAR介导，这些数据显示突触外NMDAR功能的变化与癫痫表达的改变呈反比关系。
We showed previously that electrographic seizures involving dentate granule cells in organotypic hippocampal slice cultures were dramatically reduced following chronic treatment with the NR2B-selective antagonist, Ro25,6981, but were increased following chronic treatment with the high-affinity competitive antagonist, APV. To begin to investigate the potential mechanisms underlying the differential effects of NMDAR antagonists on seizures, electrophysiological experiments were conducted in dentate granule cells in hippocampal slice cultures treated for the entire 17–21 day culture period with vehicle, Ro25,6981 or D-APV. Initial experiments revealed a lack of an association between mEPSC measures and seizures suggesting that shifts in mEPSC were unlikely to account for the differential effects of D-APV and Ro25,6981 on seizures. However, the amplitude of tonic NMDAR-mediated currents was reduced in cultures treated chronically with D-APV and dramatically enhanced in cultures treated chronically with Ro25,6981. Since tonic NMDAR currents are mediated primarily by extrasynaptic NMDAR, these data show an inverse relationship between changes in extrasynaptic NMDAR function and alterations in seizure expression.
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DOI：
10.1073/pnas.96.20.11631
发表时间：
1999-09-28
影响因子：
11.1
作者：
McKinney, RA;Lüthi, A;Thompson, SM
通讯作者：
Thompson, SM
影响因子：
4.7
作者：
Wang, XM;Bausch, SB
通讯作者：
Bausch, SB
影响因子：
5.5
作者：
Le Meur, Karim;Galante, Micaela;Audinat, Etienne
通讯作者：
Audinat, Etienne
影响因子：
56.9
作者：
OLNEY, JW;LABRUYERE, J;PRICE, MT
通讯作者：
PRICE, MT
DOI：
10.1007/978-1-60327-263-6_11
发表时间：
2009-01-01
期刊：
ANIMAL MODELS OF EPILEPSY: METHODS AND INNOVATIONS
影响因子：
--
作者：
Bausch, Suzanne B.
通讯作者：
Bausch, Suzanne B.