Ziprasidone ameliorates anxiety-like behaviors in a rat model of PTSD and up-regulates neurogenesis in the hippocampus and hippocampus-derived neural stem cells
Ziprasidone ameliorates anxiety-like behaviors in a rat model of PTSD and up-regulates neurogenesis in the hippocampus and hippocampus-derived neural stem cells
复制标题
齐拉西酮改善 PTSD 大鼠模型的焦虑样行为，并上调海马和海马衍生神经干细胞的神经发生
DOI：
10.1016/j.bbr.2013.01.032
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发表时间：
2013-05-01
影响因子：
2.7
通讯作者：
Tan, Qingrong
中科院分区：
文献类型：
--
作者：
Peng, Zhengwu;Zhang, Ruiguo;Tan, Qingrong
齐拉西酮是一种广泛使用的非典型抗精神病药物，已被证明对创伤后应激障碍（PTSD）患者有治疗作用，但其潜在机制仍知之甚少。一种可能的解释是齐拉西酮的神经保护和神经发生作用可以减弱海马中发生的神经元凋亡。为了验证这一假设，本研究旨在评估齐拉西酮治疗对雄性Sprague-Dawley大鼠焦虑样行为、海马神经发生和体内/体外pERK 1/2和Bcl-2表达的影响。该方法涉及3个不同的实验，研究还包括齐拉西酮治疗中U 0126干扰的评估。结果发现，齐拉西酮不仅能逆转大鼠在单一长时应激模型下的焦虑样行为，而且能恢复海马细胞增殖及pERK 1/2和Bcl-2蛋白表达。此外，低浓度的齐拉西酮促进了体外培养的拟南芥源性神经干细胞（NSCs）的增殖，并增加了NSCs中pERK 1/2和BcL-2的水平。有趣的是，观察到的齐拉西酮的作用被U 0126抑制。这些数据支持使用齐拉西酮治疗PTSD，并表明ERK 1/2信号级联反应的变化可能在PTSD的病理生理学及其治疗方式中发挥关键作用。需要进一步的研究来阐明应激相关疾病的病理生理学中涉及的详细信号级联，并证实齐拉西酮在抗PTSD治疗中的疗效。(c)2013爱思唯尔有限公司版权所有。
Ziprasidone, a widely used atypical antipsychotic drug, has been demonstrated to have therapeutic effects in patients with post-traumatic stress disorder (PTSD), but its underlying mechanisms remain poorly understood. One possible explanation is that the neuroprotective and neurogenetic actions of ziprasidone can attenuate the neuronal apoptosis which occurs in the hippocampus. To test this hypothesis, the present study was designed to assess the effects of ziprasidone treatment on anxiety-like behaviors, hippocampal neurogenesis, and invivo/in vitro expression of pERK1/2 and Bcl-2 in male Sprague-Dawley rats. The methodology involved 3 different experiments, and the investigations also included the assessment of U0126 interference in ziprasidone treatment. It was found that the in vivo, administration of ziprasidone not only reversed the anxiety-like behaviors in rats that exposed to an enhanced single prolonged stress paradigm, but also restored the proliferation and the protein expression of pERK1/2 and Bcl-2 in the hippocampus of these rats. Also, mild concentrations of ziprasidone promoted the in vitro proliferation of hippocampal-derived neural stem cells (NSCs) and increased the levels of pERK1/2 and BcL-2 in NSCs. Interestingly, the observed effects of ziprasidone were inhibited by U0126. These data support the use of ziprasidone for the treatment of PTSD and indicate that the changes in the ERK1/2 signaling cascade may play a critical role in the pathophysiology of PTSD and its treatment modalities. Further investigations are needed to elucidate the detailed signal cascades involved in the pathophysiology of stress-related disorders, and confirm the efficacy of ziprasidone in anti-PTSD treatment. (c) 2013 Elsevier B.V. All rights reserved.