d-Leucine: Evaluation in an epilepsy model.
d-Leucine: Evaluation in an epilepsy model.
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DOI：
10.1016/j.yebeh.2017.09.003
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Hartman AL
中科院分区：
文献类型：
--
作者：
Holden K;Hartman AL
目前的药物不能为近三分之一的癫痫患者提供足够的癫痫控制。需要新的选择来解决这一治疗差距。我们最近发现，非典型氨基酸D-亮氨酸对小鼠急性诱发癫痫发作有保护作用，但其在慢性癫痫发作中的作用尚未探讨。我们假设，D-亮氨酸将防止自发复发性癫痫发作。我们还研究了缺乏先前描述的D-亮氨酸受体（Tas 1 R2/R3）的小鼠是否会受到保护，免受急性诱导的癫痫发作。在D-亮氨酸治疗之前、期间和之后，对雄性FVB/NJ小鼠进行红藻氨酸诱导的癫痫持续状态，并通过视频EEG（手术植入电极）进行监测4周。Tas 1 R2/R3基因敲除小鼠和对照小鼠进行最大电击阈值（MES-T）和6 Hz测试。D-亮氨酸治疗组癫痫发作的日历天数或癫痫发作频率无差异。在探索性分析中，用D-亮氨酸治疗的小鼠具有较少数量的癫痫发作的黑暗周期。Tas 1 R2/R3基因敲除小鼠在MES-T测试中癫痫发作阈值升高，但在6 Hz测试中没有。D-亮氨酸治疗对红藻氨酸诱导的癫痫持续状态后的慢性癫痫发作无效，但在黑暗周期期间有一定疗效。由于D-亮氨酸高度集中在松果体，这些数据表明，D-亮氨酸可能是有用的，作为一种工具，研究癫痫的昼夜节律模式。Tas 1 R2/R3受体的缺失在MES-T试验中保护了癫痫发作，因此可能是治疗癫痫发作的新靶点。
Current medicines do not provide sufficient seizure control for nearly one third of patients with epilepsy. New options are needed to address this treatment gap. We recently found that the atypical amino acid D-leucine protected against acutely-induced seizures in mice but its effect in chronic seizures has not been explored. We hypothesized that D-leucine would protect against spontaneous recurrent seizures. We also investigated whether mice lacking a previously-described D-leucine receptor (Tas1R2/R3) would be protected against acutely-induced seizures. Male FVB/NJ mice were subjected to kainic acid-induced status epilepticus and monitored by video EEG (surgically implanted electrodes) for 4 weeks before, during, and after treatment with D-leucine. Tas1R2/R3 knockout mice and controls underwent the maximal electroshock threshold (MES-T) and 6 Hz tests. There was no difference in number of calendar days with seizures or seizure frequency with D-leucine treatment. In an exploratory analysis, mice treated with D-leucine had a lower number of dark cycles with seizures. Tas1R2/R3 knockout mice had elevated seizure thresholds in the MES-T test but not the 6 Hz test. D-leucine treatment was ineffective against chronic seizures after kainic acid-induced status epilepticus but there was some efficacy during the dark cycle. Because D-leucine is highly concentrated in the pineal gland, these data suggest that D-leucine may be useful as a tool for studying circadian patterns in epilepsy. Deletion of the Tas1R2/R3 receptor protected against seizures in the MES-T test and therefore may be a novel target for treating seizures.
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松果体节律的昼夜节律调节。
影响因子：
4.1
作者：
Borjigin, Jimo;Zhang, L. Samantha;Calinescu, Anda-Alexandra
通讯作者：
Calinescu, Anda-Alexandra
DOI：
10.1016/s0304-4165(96)00095-5
发表时间：
1997-03-15
影响因子：
3
作者：
Hamase, K;Homma, H;Imai, K
通讯作者：
Imai, K
影响因子：
--
作者：
Bazil, CW;Castro, LHM;Walczak, TS
通讯作者：
Walczak, TS
影响因子：
2.9
作者：
Hamase, K;Inoue, T;Zaitsu, K
通讯作者：
Zaitsu, K
影响因子：
3.5
作者：
Hamase, K;Homma, H;Imai, K
通讯作者：
Imai, K