Kraus Larissa, Hetsch Florian, Schneider Ulf C, Radbruch Helena, Holtkamp Martin, Meier Jochen C, Fidzinski Pawel
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology with Experimental Neurology, Berlin, Germany.
Berlin Institute of Health (BIH), Zoologisches Institut, Technische Universität Braunschweig, Braunschweig, Germany.
Front Mol Neurosci. 2019 Sep 6;12:209. doi: 10.3389/fnmol.2019.00209. eCollection 2019.
Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy with about 30% of patients developing pharmacoresistance. These patients continue to suffer from seizures despite polytherapy with antiepileptic drugs (AEDs) and have an increased risk for premature death, thus requiring further efforts for the development of new antiepileptic therapies. The molecule dimethylethanolamine (DMEA) has been tested as a potential treatment in various neurological diseases, albeit the functional mechanism of action was never fully understood. In this study, we investigated the effects of DMEA on neuronal activity in single-cell recordings of primary neuronal cultures. DMEA decreased the frequency of spontaneous synaptic events in a concentration-dependent manner with no apparent effect on resting membrane potential (RMP) or action potential (AP) threshold. We further tested whether DMEA can exert antiepileptic effects in human brain tissue . We analyzed the effect of DMEA on epileptiform activity in the CA1 region of the resected hippocampus of TLE patients by recording extracellular field potentials in the pyramidal cell layer. Epileptiform burst activity in resected hippocampal tissue from TLE patients remained stable over several hours and was pharmacologically suppressed by lacosamide, demonstrating the applicability of our platform to test antiepileptic efficacy. Similar to lacosamide, DMEA also suppressed epileptiform activity in the majority of samples, albeit with variable interindividual effects. In conclusion, DMEA might present a new approach for treatment in pharmacoresistant TLE and further studies will be required to identify its exact mechanism of action and the involved molecular targets.
颞叶癫痫（TLE）是局灶性癫痫最常见的形式，约30%的患者会产生药物抵抗。尽管使用抗癫痫药物（AEDs）进行了联合治疗，这些患者仍继续遭受癫痫发作，并且过早死亡的风险增加，因此需要进一步努力开发新的抗癫痫疗法。二甲基乙醇胺（DMEA）分子已作为一种潜在治疗方法在各种神经系统疾病中进行了测试，尽管其功能作用机制从未被完全理解。在本研究中，我们在原代神经元培养物的单细胞记录中研究了DMEA对神经元活动的影响。DMEA以浓度依赖性方式降低自发突触事件的频率，对静息膜电位（RMP）或动作电位（AP）阈值无明显影响。我们进一步测试了DMEA是否能在人脑组织中发挥抗癫痫作用。我们通过记录锥体细胞层的细胞外场电位，分析了DMEA对TLE患者切除海马CA1区癫痫样活动的影响。来自TLE患者切除海马组织中的癫痫样爆发活动在数小时内保持稳定，并被拉科酰胺药理学抑制，证明了我们的平台在测试抗癫痫疗效方面的适用性。与拉科酰胺类似，DMEA也在大多数样本中抑制了癫痫样活动，尽管个体间存在不同的效应。总之，DMEA可能为药物抵抗性TLE的治疗提供一种新方法，需要进一步研究以确定其确切作用机制和涉及的分子靶点。
