Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice.
Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice.
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作者：
West PJ;Saunders GW;Remigio GJ;Wilcox KS;White HS
认知共病越来越多地被认为是癫痫的一个平等（或甚至更禁用）方面。此外，一些抗癫痫药物（ASD）的作用可能会影响学习和记忆。因此，NINDS癫痫研究基准要求实施标准化方案，以筛查ASD的认知共病改善或恶化。长时程增强（LTP）是研究突触可塑性及其与学习记忆关系的一个广泛应用的模型。虽然一些ASD对LTP的影响已经过研究，但这些研究都没有采用生理学相关的诱导刺激，如θ-突发刺激（TBS）。为了系统地评估使用生理学相关刺激方案在同一制剂中的多个ASD的影响，我们检查了一系列现有ASD对TBS诱导的C57 BL/6小鼠体外脑切片CA 1区LTP的影响，这些脑切片在正常或基于蔗糖的ACSF中制备。使用标准或基于蔗糖的ACSF制备含有背侧海马的冠状脑切片。使用Scientific Slicemaster高通量记录系统一次从四个切片获得记录。接触ASD的切片与作为对照的另一侧半球的切片配对。记录场兴奋性突触后电位（fEPSP），并在诱导刺激前通过浴灌注20分钟将所有ASD应用于切片。LTP由TBS或高频刺激（HFS）诱导。检查了以下ASD：100 µM苯巴比妥（PB）、80 µM苯妥英（PHT）、50 µM卡马西平（CBZ）、600 µM丙戊酸盐（VPA）、60 µM托吡酯（TPM）、60 µM拉莫三嗪（LTG）、100 µM左乙拉西坦（LEV）、10 µM依佐加滨（EZG）和30 µM噻加滨（TGB）。在电压门控钠通道抑制剂中，CBZ显著减弱TBS诱导的LTP，PHT减弱TBS诱导的LTP和强直后增强（PTP），LTG不能影响LTP，但确实减弱PTP。调节GABA能突触传递的ASD，如PB和TGB，显著减弱了在蔗糖基ACSF中制备的脑切片中的LTP，而不是标准ACSF。第三代ASD，如LEV和TPM，不影响ACSF或蔗糖制备的脑切片的LTP。虽然EZG未能影响LTP，但在两种切片条件下均显著减弱PTP。在TBS和HFS实验中，VPA对C57 BL/6小鼠和Sprague道利大鼠CA 1区LTP均无影响。然而，VPA确实减弱了TBS诱导的齿状回（DG）LTP。
Cognitive comorbidities are increasingly recognized as an equal (or even more disabling) aspect of epilepsy. Additionally, the actions of some antiseizure drugs (ASDs) can impact learning and memory. Accordingly, the NINDS epilepsy research benchmarks call for the implementation of standardized protocols for screening ASDs for their amelioration or exacerbation of cognitive comorbidities. Long-term potentiation (LTP) is a widely used model for investigating synaptic plasticity and its relationship to learning and memory. While the effects of some ASDs on LTP have been examined, none of these studies employed physiologically relevant induction stimuli such as theta-burst stimulation (TBS). To systematically evaluate the effects of multiple ASDs in the same preparation using physiologically relevant stimulation protocols, we examined the effects of a broad panel of existing ASDs on TBS-induced LTP in area CA1 of in-vitro brain slices, prepared in either normal or sucrose-based ACSF, from C57BL/6 mice. Coronal brain slices containing the dorsal hippocampus were made using either standard or sucrose-based ACSF. Recordings were obtained from four slices at a time using the Scientifica Slicemaster high throughput recording system. Slices exposed to ASDs were paired with slices from the opposite hemisphere that served as controls. Field excitatory post-synaptic potentials (fEPSPs) were recorded, and all ASDs were applied to slices by bath perfusion for 20 minutes prior to the induction stimulus. LTP was induced by TBS or by high-frequency stimulation (HFS). The following ASDs were examined: 100 µM phenobarbital (PB), 80 µM phenytoin (PHT), 50 µM carbamazepine (CBZ), 600 µM valproate (VPA), 60 µM topiramate (TPM), 60 µM lamotrigine (LTG), 100 µM levetiracetam (LEV), 10 µM ezogabine (EZG), and 30 µM tiagabine (TGB). Among voltage-gated sodium channel inhibitors, CBZ significantly attenuated TBS-induced LTP, PHT attenuated both TBS-induced LTP and post-tetanic potentiation (PTP), and LTG failed to affect LTP but did attenuate PTP. ASDs that modulate GABAergic synaptic transmission, such as PB and TGB, significantly attenuated LTP in brain slices prepared in sucrose-based ACSF but not standard ACSF. Third generation ASDs, such as LEV and TPM, did not affect LTP in ACSF- or sucrose-prepared brain slices. While EZG failed to affect LTP, it did significantly attenuate PTP under both slicing conditions. VPA failed to affect LTP in area CA1, both in C57BL/6 mice and Sprague Dawley rats, using TBS or HFS. However, VPA did attenuate TBS-induced LTP in the dentate gyrus (DG).
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影响因子：
3.8
作者：
Lee, GYP;Brown, LM;Teyler, TJ
通讯作者：
Teyler, TJ
影响因子：
7.3
作者：
Eckstein-Ludwig, U;Fei, J;Schwarz, W
通讯作者：
Schwarz, W
影响因子：
9.9
作者：
MEADOR, KJ;LORING, DW;KING, DW
通讯作者：
KING, DW
DOI：
10.1124/jpet.105.083923
发表时间：
2005-07-01
影响因子：
3.5
作者：
Korsgaard, MPG;Hartz, BP;Mirza, NR
通讯作者：
Mirza, NR
影响因子：
2.6
作者：
Lamberty, Yves;Margineanu, Doru Georg;Klitgaard, Henrik
通讯作者：
Klitgaard, Henrik