Studies on the animal model of post-stroke depression and application of antipsychotic aripiprazole
Studies on the animal model of post-stroke depression and application of antipsychotic aripiprazole
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DOI：
10.1016/j.bbr.2015.03.062
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发表时间：
2015-07-01
影响因子：
2.7
通讯作者：
Choi, Byung Tae
中科院分区：
文献类型：
--
作者：
Kim, Yu Ri;Kim, Ha Neui;Choi, Byung Tae
我们研究了是否可以通过额外的慢性轻度应激（CMS）程序来建立缺血性中风后抑郁症动物模型的问题。对小鼠 CMS、左大脑中动脉闭塞 (MCAO) 和 MCAO 后 CMS (MCAO + CMS) 的抑郁症进行行为和组织病理学分析。在所有涉及旷场、蔗糖偏好、强迫游泳和莫里斯水迷宫测试的抑郁筛选测试中，MCAO + CMS 小鼠比 MCAO 小鼠表现出更显着的抑郁行为。与 CMS 相比，MCAO + CMS 小鼠在强迫游泳和莫里斯水迷宫测试中也表现出明显的缺陷。在组织病理学分析中，与CMS相比，MCAO治疗小鼠的纹状体和中脑出现明显的萎缩变化。与仅用 CMS 和 MCAO 治疗的小鼠相比，MCAO + CMS 小鼠的纹状体和海马中的增殖和分化神经元细胞减少，中脑多巴胺能神经元损伤。用阿立哌唑治疗 MCAO + CMS 小鼠导致所有检查的抑郁行为减少，特别是在莫里斯水迷宫测试中。还证明了中脑多巴胺能神经元损伤的恢复和海马神经发生的增强。我们的结果表明，与单独使用 CMS 或 MCAO 治疗的小鼠相比，缺血性中风后的 CMS 可通过原发病变和继发性病灶外部位的神经变性以及神经发生的退化而导致严重的抑郁样行为，并且这些行为和组织病理学变化可通过阿立哌唑治疗逆转。因此，抗精神病药的辅助治疗可能通过 CMS 治疗的缺血小鼠的神经保护和神经发生发挥其抗抑郁作用。 (C) 2015 Elsevier B.V. 保留所有权利。
We investigated the question of whether an animal model of post-stroke depression in ischemic stroke can be developed by additional chronic mild stress (CMS) procedures. Behavioral and histopathological analysis was performed for examination of the depressive disorders in CMS, left middle cerebral artery occlusion (MCAO) and CMS after MCAO (MCAO + CMS) in mice. In all depressant screening tests involving open field, sucrose preference, forced swim and Morris water maze test, MCAO + CMS mice showed more significant depressive behaviors than MCAO mice. MCAO + CMS mice also showed distinct deficits in forced swim and Morris water maze test compared with CMS. In the histopathological analysis, prominent atrophic changes were seen in the striatum and midbrain of MCAO treated mice compared with CMS. MCAO + CMS mice showed a decrease of proliferative and differentiated neuronal cells in the striatum and hippocampus with dopaminergic neuronal injuries in the midbrain as compared with CMS and MCAO alone treated mice. Treatment of MCAO + CMS mice with aripiprazole resulted in reduction of all depressive behaviors examined, particularly in the Morris water maze test. Recovered dopaminergic neuronal injuries in the midbrain and enhanced neurogenesis in the hippocampus were also demonstrated. Our results suggest that CMS after ischemic stroke can lead to severe depressive-like behavior compared with CMS or MCAO alone treated mice via neurodegeneration in the primary lesion and secondary extrafocal sites and degradation of neurogenesis, and these behavioral and histopathological changes are reversed by treatment with aripiprazole. Thus adjunct therapy with an antipsychotic may exert its antidepressant effects via neuroprotection and neurogenesis in CMS-treated ischemic mice. (C) 2015 Elsevier B.V. All rights reserved.