Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.
Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.
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DOI：
10.1016/j.biopsych.2017.11.019
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发表时间：
2018-05-15
影响因子：
10.6
通讯作者：
Risbrough VB
中科院分区：
文献类型：
--
作者：
Deslauriers J;Toth M;Der-Avakian A;Risbrough VB
提高创伤后应激障碍（PTSD）动物模型的可预测性需要临床和临床前科学家之间的积极合作。建模PTSD是具有挑战性的，因为它是具有20多种症状的异质性疾病。临床研究越来越多地利用客观的生物学措施（例如成像，外周生物标志物）或非语言行为/生理反应来补充口头报告的症状。这种向更客观可测量的表型的转变使得当前PTSD动物模型的改进成为可能，并支持跨物种的同源测量的并入。我们回顾了超过600篇文章，以检查当前啮齿动物模型除了行为表型之外还探测PTSD生物表型（例如睡眠障碍，海马和恐惧回路功能障碍，炎症，糖皮质激素受体超敏反应）的能力。大多数模型可靠地产生持久的广泛性焦虑和/或抑郁样行为，以及过度活跃的恐惧回路，糖皮质激素受体超敏反应和对慢性SSRIs的反应。虽然一些范例探讨恐惧条件反射/灭绝和/或利用外周免疫，睡眠和非侵入性成像措施，我们认为应该更多地纳入，以提高翻译。在女性中，在整个生命周期的不同年龄，或应激后表型的时间轨迹，这将告知模型效用和治疗研究的实验设计的数据很少。总体而言，临床前（和临床）PTSD研究人员越来越多地采用同源生物学措施来评估风险，反应和治疗结果的标志物。这一转变令人兴奋，因为我们和许多其他人希望它不仅能支持药物疗效从动物模型到临床试验的转化，而且可能提高II期临床试验的可预测性。
Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging as it is heterogeneous disorder with 20+ symptoms. Clinical research is increasingly utilizing objective biological measures (e.g. imaging, peripheral biomarkers) or non-verbal behaviors/physiological responses to complement verbally reported symptoms. This shift toward more objectively measurable phenotypes enables refinement of current animal models of PTSD, and supports incorporation of homologous measures across species. We reviewed >600 articles to examine the ability of current rodent models to probe biological phenotypes of PTSD (e.g. sleep disturbances, hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor hypersensitivity) in addition to behavioral phenotypes. Most models reliably produced enduring generalized anxiety- and/or depression-like behaviors, as well as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and response to chronic SSRIs. Although a few paradigms probed fear conditioning/extinction and/or utilized peripheral immune, sleep, and non-invasive imaging measures, which we argue should be incorporated more to enhance translation. There was little data in females, at different ages across the lifespan, or on temporal trajectories of phenotypes post-stress, which would inform model utility and experimental design for treatment studies. Overall, preclinical (and clinical) PTSD researchers are increasingly incorporating homologous biological measures to assess markers of risk, response and treatment outcome. This shift is exciting, as we and many others hope it will support translation of drug efficacy not only from animal models to clinical trials, but potentially improve predictability of stageII for stageIII clinical trials.
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DOI：
10.3109/10253890.2014.910649
发表时间：
2014-05-01
影响因子：
2.3
作者：
Cotella, Evelin M.;Durando, Patricia E.;Suarez, Marta M.
通讯作者：
Suarez, Marta M.
DOI：
10.1186/2045-5380-1-9
发表时间：
2011-11-07
期刊：
Biology of mood & anxiety disorders
影响因子：
--
作者：
Belzung C;Lemoine M
通讯作者：
Lemoine M
影响因子：
10.6
作者：
Brachman RA;McGowan JC;Perusini JN;Lim SC;Pham TH;Faye C;Gardier AM;Mendez-David I;David DJ;Hen R;Denny CA
通讯作者：
Denny CA
影响因子：
3.2
作者：
Cohen, H.;Kaplan, Z.;Zohar, J.
通讯作者：
Zohar, J.
影响因子：
2.9
作者：
Björkqvist, K
通讯作者：
Björkqvist, K