ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum
ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum
复制标题
DOI：
10.1016/j.jphs.2022.01.009
复制
发表时间：
2022-02-04
影响因子：
3.5
通讯作者：
Tan-No, Koichi
中科院分区：
文献类型：
--
作者：
Nakagawasai, Osamu;Takahashi, Kohei;Tan-No, Koichi
细胞外信号调节蛋白激酶5（ERK 5）具有多种生理功能。然而，ERK 5在用非法药物如甲基苯丙胺（METH）治疗小鼠中的生理作用仍然未知。我们发现，用METH治疗的小鼠表现出多动症，并增加了纹状体中的p-ERK 5和Iba 1（小胶质细胞标记物）水平。此外，这些变化被ERK 5抑制剂BIX 02189预处理抑制。结果表明，甲基苯丙胺诱导的过度活跃与纹状体中通过p-ERK 5激活小胶质细胞有关。因此，中枢神经系统中的ERK 5通路组分是预防METH成瘾的潜在治疗靶点。(c)2022作者Elsevier B. V.代表日本药理学会制作和主办。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：creativecommons.org/ licenses/by-nc-nd/4.0/）。
Extracellular signal-regulated protein kinase 5 (ERK5) has various physiological functions. However, the physiological role of ERK5 in the treatment of mice with an illicit drug such as methamphetamine (METH) remains unknown. We revealed that mice treated with METH showed hyperactivity, and increased p-ERK5 and Iba1 (a microglia marker) levels in the striatum. Additionally, these changes were inhibited by pretreatment with the ERK5 inhibitor BIX02189. The results suggest that METH-induced hyperactivity is associated with the activation of microglia via p-ERK5 in the striatum. Thus, the ERK5 pathway components in the central nervous system are potential therapeutic targets for preventing METH addiction. (c) 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).