Levetiracetam Differentially Alters CD95 Expression of Neuronal Cells and the Mitochondrial Membrane Potential of Immune and Neuronal Cells in vitro.
Levetiracetam Differentially Alters CD95 Expression of Neuronal Cells and the Mitochondrial Membrane Potential of Immune and Neuronal Cells in vitro.
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DOI：
10.3389/fneur.2014.00017
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发表时间：
2014
影响因子：
3.4
通讯作者：
Newell-Rogers MK
中科院分区：
文献类型：
--
作者：
Rogers SK;Shapiro LA;Tobin RP;Tow B;Zuzek A;Mukherjee S;Newell-Rogers MK
癫痫是一种神经系统疾病，影响全球超过1亿人。左乙拉西坦，无论是单独，作为单一疗法，或作为预防性治疗，被广泛用于控制某些类型的癫痫发作。尽管其作为一种相对安全有效的抗惊厥治疗选择越来越受欢迎，但其作用机制仍知之甚少。研究表明，神经元，神经胶质和免疫作用机制。了解左乙拉西坦的确切作用机制将有助于了解癫痫发作和癫痫的过程。此外，充分了解这些机制将有助于创造更有效的治疗方法，同时最大限度地减少副作用。目前的研究检查了左乙拉西坦对体外神经元和非神经元细胞线粒体膜电位的影响，以确定左乙拉西坦是否影响这些细胞类型的代谢过程。此外，本研究试图通过确定左乙拉西坦是否改变免疫受体-配体对的表达来解决可能的免疫介导机制。结果显示，左乙拉西坦诱导经NGF处理的C17.2神经元细胞上的CD 95和CD 178的表达。结果还表明，左乙拉西坦在神经生长因子存在下增加C17.2神经元细胞上的线粒体膜电位。相反，左乙拉西坦降低脾细胞的线粒体膜电位，这种作用依赖于完整的不变链，因此涉及免疫细胞相互作用。这些结果表明，左乙拉西坦的神经元和非神经元抗癫痫活性均涉及对能量代谢的控制，更具体地说，mΔ ε。未来的研究需要进一步研究这种潜在的作用机制。
Epilepsy is a neurological seizure disorder that affects over 100 million people worldwide. Levetiracetam, either alone, as monotherapy, or as adjunctive treatment, is widely used to control certain types of seizures. Despite its increasing popularity as a relatively safe and effective anti-convulsive treatment option, its mechanism(s) of action are poorly understood. Studies have suggested neuronal, glial, and immune mechanisms of action. Understanding the precise mechanisms of action of levetiracetam would be extremely beneficial in helping to understand the processes involved in seizure generation and epilepsy. Moreover, a full understanding of these mechanisms would help to create more efficacious treatments while minimizing side-effects. The current study examined the effects of levetiracetam on the mitochondrial membrane potential of neuronal and non-neuronal cells, in vitro, in order to determine if levetiracetam influences metabolic processes in these cell types. In addition, this study sought to address possible immune-mediated mechanisms by determining if levetiracetam alters the expression of immune receptor–ligand pairs. The results show that levetiracetam induces expression of CD95 and CD178 on NGF-treated C17.2 neuronal cells. The results also show that levetiracetam increases mitochondrial membrane potential on C17.2 neuronal cells in the presence of nerve growth factor. In contrast, levetiracetam decreases the mitochondrial membrane potential of splenocytes and this effect was dependent on intact invariant chain, thus implicating immune cell interactions. These results suggest that both neuronal and non-neuronal anti-epileptic activities of levetiracetam involve control over energy metabolism, more specifically, mΔΨ. Future studies are needed to further investigate this potential mechanism of action.
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影响因子：
2.9
作者：
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通讯作者：
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5.6
作者：
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