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低浓度二甲基亚砜(DMSO)调节 4-氨基吡啶体外模型中的癫痫样同步。

Low concentration dimethyl sulfoxide (DMSO) modulates epileptiform synchronization in the 4-aminopyridine in vitro model.

机构信息

Montreal Neurological Institute-Hospital and Departments of Neurology & Neurosurgery and McGill University, 3801 University Street, Montréal, Québec H3A 2B4, Canada; Department of Physiology, McGill University, 3801 University Street, Montréal, Québec H3A 2B4, Canada.

Department of Psychology, McGill University, 2001 McGill College Ave, Montreal, Quebec H3A 1G1, Canada.

出版信息

J Neurosci Methods. 2024 Nov;411:110255. doi: 10.1016/j.jneumeth.2024.110255. Epub 2024 Aug 17.

Abstract

Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro. Therefore, we investigated here the effect of 0.03 % and 0.06 % DMSO, which are 10-50 times lower than what usually employed in previous studies, in the 4-aminopyridine (4AP) model of epileptiform synchronization in male mouse brain slices. We found that 0.03 % and 0.06 % DMSO increase 4AP-induced ictal discharge rate, while 0.06 % DMSO decreases ictal discharge duration. Our results suggest that the effects of DMSO on neuronal excitability deserve further analysis and that investigators need to be aware of its confounding effect as a solvent, even at very low concentrations.

摘要

二甲基亚砜(DMSO)因其具有偶极和非质子特性,常被用于溶解水溶性差的药物。它也是许多药理学研究中的载体。然而,据报道 DMSO 可在人类患者中引发癫痫发作,降低体内癫痫发作阈值,并在体外调节离子受体活性。因此,我们在此研究了浓度分别为 0.03%和 0.06%的 DMSO(远低于以往研究中常用的浓度 10-50 倍)对雄性小鼠脑切片中 4-氨基吡啶(4AP)致癫痫样同步模型的影响。我们发现 0.03%和 0.06%的 DMSO 增加了 4AP 诱导的癫痫发作放电率,而 0.06%的 DMSO 则缩短了癫痫发作持续时间。我们的结果表明,DMSO 对神经元兴奋性的影响值得进一步分析,研究人员需要意识到其作为溶剂的混杂效应,即使在非常低的浓度下也是如此。

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