Translational relevance of behavioral, neural, and electroencephalographic profiles in a mouse model of post-traumatic stress disorder.
Translational relevance of behavioral, neural, and electroencephalographic profiles in a mouse model of post-traumatic stress disorder.
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创伤后应激障碍小鼠模型中行为、神经和脑电图谱的转化相关性
DOI：
10.1016/j.ynstr.2021.100391
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发表时间：
2021-11
影响因子：
5
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Xi K;Huang X;Liu T;Liu Y;Mao H;Wang M;Feng D;Wang W;Guo B;Wu S
创伤后应激障碍（PTSD）是一种由痛苦事件引发的严重的、长期的心理障碍。PTSD的神经基础和潜在机制尚不完全清楚。因此，使用可靠的动物模型来模拟患者的症状来确定PTSD的病理是很重要的。然而，缺乏创伤后应激障碍动物模型临床相关性的证据使得从翻译角度解释临床前研究变得困难。在这项研究中，我们对单次长时间应激和足电（SPS&S）小鼠模型的行为、神经元、神经胶质和脑电图（EEG）进行了全面筛选。基于PTSD的临床特征，我们观察到SPS&S模型小鼠对创伤相关环境的恐惧和过度反应持续时间超过14天。小鼠对听觉刺激引起的恐惧记忆消退表现出了缺陷性和强烈的抵抗力，同时也表现出视觉刺激引起的先天恐惧增强，并伴有恐惧和焦虑。此外，ptsd相关脑区的神经元、星形胶质细胞和小胶质细胞被激活，支持异常的脑激活和神经免疫变化。脑电图评估也显示皮质区域之间的功率下降和耦合强度受损。这些结果表明，SPS&S小鼠模型概括了PTSD患者的行为症状以及神经和脑电图特征，证明了该小鼠模型的临床前使用是合理的。
Post-traumatic stress disorder (PTSD) is a severe, long-term psychological disorder triggered by distressing events. The neural basis and underlying mechanisms of PTSD are not completely understood. Therefore, it is important to determine the pathology of PTSD using reliable animal models that mimic the symptoms of patients. However, the lack of evidence on the clinical relevance of PTSD animal models makes it difficult to interpret preclinical studies from a translational perspective. In this study, we performed a comprehensive screening of the behavioral, neuronal, glial, and electroencephalographic (EEG) profiles in the single prolonged stress and electric foot shock (SPS&S) mouse model. Based on the clinical features of PTSD, we observed fearful and excessive responses to trauma-related environments in the SPS&S mouse model that lasted longer than 14 days. The mice exhibited a defective and strong resistance to the extinction of fear memories caused by auditory cues and also showed enhanced innate fear induced by visual stimuli with concomitant phobias and anxiety. Furthermore, neurons, astrocytes, and microglia in PTSD-related brain regions were activated, supporting abnormal brain activation and neuroimmune changes. EEG assessment also revealed decreased power and impaired coupling strength between cortical regions. These results demonstrated that the SPS&S mouse model recapitulates the behavioral symptoms as well as neural and EEG profiles of PTSD patients, justifying the preclinical use of this mouse model.
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DOI：
10.1038/s41583-018-0039-7
发表时间：
2018-09
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Fenster RJ;Lebois LAM;Ressler KJ;Suh J
通讯作者：
Suh J
2-芳基烯丙基甘油信号传导会损害短期恐惧灭绝。
影响因子：
6.8
作者：
Hartley ND;Gunduz-Cinar O;Halladay L;Bukalo O;Holmes A;Patel S
通讯作者：
Patel S
影响因子：
25.8
作者：
Eraly, Satish A.;Nievergelt, Caroline M.;Maihofer, Adam X.;Barkauskas, Donald A.;Biswas, Nilima;Agorastos, Agorastos;O'Connor, Daniel T.;Baker, Dewleen G.
通讯作者：
Baker, Dewleen G.
影响因子：
3
作者：
Ferland-Beckham C;Chaby LE;Daskalakis NP;Knox D;Liberzon I;Lim MM;McIntyre C;Perrine SA;Risbrough VB;Sabban EL;Jeromin A;Haas M
通讯作者：
Haas M
影响因子：
3.7
作者：
Daskalakis, Nikolaos P.;Yehuda, Rachel;Diamond, David M.
通讯作者：
Diamond, David M.