Building a framework to optimize animal models of maternal immune activation: Like your ongoing home improvements, it's a work in progress.
Building a framework to optimize animal models of maternal immune activation: Like your ongoing home improvements, it's a work in progress.
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建立一个框架来优化母体免疫激活的动物模型：就像您正在进行的家庭装修一样，这是一项正在进行的工作。
DOI：
10.1016/j.bbi.2018.10.011
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kentner,AmandaC
中科院分区：
文献类型：
--
作者：
Roderick,RylandC;Kentner,AmandaC
母体免疫激活（mIA）的动物模型已经出现，对于靶向神经精神疾病的分子机制来说既具有翻译相关性又至关重要。重要的是，与 mIA 相关的实验结果因特定研究成分（例如免疫原、剂量、物种/菌株）和其他饲养考虑因素而异，这些考虑因素通常报道不足，但对免疫反应和我们动物模型的完整性有影响（Estes 和 McAllister，2016 年；Kentner 等人，2018 年）。在本期《大脑、行为和免疫》中，Murray 等人 (2018) 为指导 mIA 模型验证和报告的最佳实践的建立奠定了基础。这些步骤为他们的实验室探索雄性和雌性后代形态测量标记的早期发育轨迹奠定了基础，揭示了 mIA 之后的性二态性表型变化。在过去的十年中，人们越来越意识到要求提高生物医学研究的科学严谨性和可重复性（Collins & Tabak，2014）以及更好的报告标准（Kilkenny 等，2010）。在此背景下，Murray 等人 (2018) 敏锐地发现了 mIA 文献中的问题，包括缺乏关于如何选择我们的研究方案的重要元素的明确标准。例如，感兴趣的免疫原和剂量、给药途径和时间表，以及所使用的具体菌株和性别。虽然这个列表并不详尽，但这些是每项 mIA 研究的基本组成部分，我们选择的理由应该是透明的和基于证据的。 Murray 及其同事（2018）强调了这一点的重要性，他们指出，虽然小鼠在 mIA 文献中最常用，但大鼠的使用也在增加。尽管一些 mIA 小鼠模型已得到验证，但相同的方法可能不适用于其他物种，因此有必要对这些模型进行进一步验证。
Animal models of maternal immune activation (mIA) have emerged as both translationally relevant and essential for targeting the molecular mechanisms underlying neuropsychiatric disorders. Importantly, experimental outcomes associated with mIA vary as a function of specific study components (eg immunogen, dose, species/strain) and other husbandry considerations that are typically under reported yet influential to the immune response and the integrity of our animal models (Estes and McAllister, 2016; Kentner et al., 2018). In this issue of Brain, Behavior, and Immunity, Murray et al (2018) lay groundwork to guide the establishment of best practices for the validation and reporting of our mIA models. These steps built the foundation from which their laboratory explored the early developmental trajectory of morphometric markers in male and female offspring, revealing sexually dimorphic phenotypic changes following mIA.Across the past decade there has been a growing consciousness calling for increased scientific rigor and reproducibility (Collins & Tabak, 2014), and for better reporting standards (Kilkenny et al., 2010) in biomedical research. Within this context, Murray et al (2018) astutely identified issues in the mIA literature including a lack of defined criteria for how important elements of our study protocols are selected. For example, the immunogens and doses of interest, administration routes and schedules, in addition to the specific strains and sex employed. While this list is not exhaustive, these are fundamental components to every mIA study and the rationale for our choices ought to be transparent and evidencebased. The importance of this is highlighted by Murray and colleagues (2018) who point out that while mice are most commonly used in the mIA literature, the use of rats is increasing too. Although some mIA mouse models have been validated, the same methods may not be appropriate for other species and further validation of these models are necessary.