Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures.
Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures.
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DOI：
10.3389/fphar.2021.766782
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发表时间：
2021
影响因子：
5.6
通讯作者：
Suzuki M
中科院分区：
文献类型：
--
作者：
Moriyama H;Nomura S;Imoto H;Inoue T;Fujiyama Y;Haji K;Maruta Y;Ishihara H;Suzuki M
癫痫是一种相对常见的疾病，但超过30%的患者患有难治性癫痫，无法充分控制或对多种药物治疗产生抗药性。因此，需要基于新发现的机制的新的抗癫痫药物。先前的一篇报道揭示了瞬时受体电位Melastatin 8(TRPM8)激活对青霉素G诱发的癫痫样放电(EDs)的抑制作用。然而，目前尚不清楚TRPM8激动剂是抑制癫痫发作，还是影响TRPM8基因敲除(TRPM8KO)小鼠的ED或癫痫发作。我们研究了TRPM8激动剂和缺乏TRPM8通道对内分泌和癫痫发作的影响。在癫痫诱导剂注射后90min或注射前30min分别注射TRPM8激动剂，麻醉下记录小鼠的皮层脑电，清醒时监测小鼠的行为。TRPM8激动剂抑制野生型(WT)小鼠的ED和癫痫发作，但对TRPM8KO小鼠无抑制作用。此外，与WT小鼠相比，TRPM8KO小鼠具有较短的EDs放电潜伏期，癫痫诱导剂可加重EDs和癫痫发作，且EDs更容易传播到对侧。这些发现表明，癫痫区域的TRPM8激活具有抗癫痫作用。
Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.
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影响因子：
2.5
作者：
Ordas, Purificacion;Hernandez-Ortego, Pablo;Senaris, Rosa
通讯作者：
Senaris, Rosa
影响因子：
4.6
作者：
Pezzoli M;Elhamdani A;Camacho S;Meystre J;González SM;le Coutre J;Markram H
通讯作者：
Markram H
影响因子：
5.3
作者：
Tsuzuki, K;Xing, H;Gu, JGG
通讯作者：
Gu, JGG
影响因子：
158.5
作者：
Kwan, P;Brodie, MJ
通讯作者：
Brodie, MJ
影响因子：
16.2
作者：
Dhaka, Ajay;Murray, Amber N.;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem