Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).
Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).
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DOI：
10.1111/ejn.15158
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Kerman IA
中科院分区：
文献类型：
--
作者：
Clinton SM;Shupe EA;Glover ME;Unroe KA;McCoy CR;Cohen JL;Kerman IA
动物模型为研究塑造大脑功能和行为的生物和环境因素提供了重要工具。通过借鉴国家精神卫生研究所领域标准(RDoC)倡议的概念，可以有效地利用这些模型，该倡议旨在描绘支撑超越精神疾病的行为异常的分子路径和神经回路。为了研究导致情绪性和应激反应的个体差异的因素，我们的实验室使用了选择性饲养的Spraogue-Dawley大鼠，这些大鼠是为了新奇探索的差异而饲养的。对新奇事物的低运动性反应和高运动性反应的选择性繁殖产生了与焦虑和抑郁相关的行为领域不同的大鼠品系，特别是RDoC负价领域，包括急性威胁、潜在威胁和损失。培育的低新奇反应者(LR)大鼠与高反应者(HR)大鼠相比，表现出高水平的行为抑制、条件性和无条件恐惧、回避、被动压力应对、快感缺乏和精神运动迟缓。HR/LR特征是可遗传的，出现在生命的头几周，似乎是由发育中的杏仁核和海马体的变化驱动的。发育中和成年HR/LR脑的表观基因组和转录图谱表明，DNA甲基化和microRNAs，以及单胺能传递(特别是多巴胺和5-羟色胺)的差异，导致了它们不同的行为表型。这项工作展示了动物模型，如HR/LR大鼠，可以有效地用于研究驱动情绪行为的神经和分子因素，这可能为更好地理解情绪障碍涉及的神经生物学机制铺平道路。对新奇事物的低运动反应和高运动反应的选择性繁殖产生了与焦虑和抑郁相关的行为领域不同的老鼠品系。低新颖性反应的大鼠表现出高水平的行为抑制、恐惧、被动压力应对和快感缺乏。分子研究确定了导致这些不同行为表型的表观遗传学和基因表达变化，这可能有助于理解情绪障碍的生物学机制。
Animal models provide important tools to study biological and environmental factors that shape brain function and behavior. These models can be effectively leveraged by drawing on concepts from the National Institute of Mental Health Research Domain Criteria (RDoC) Initiative, which aims to delineate molecular pathways and neural circuits that underpin behavioral anomalies that transcend psychiatric conditions. To study factors that contribute to individual differences in emotionality and stress reactivity, our laboratory utilized Sprague-Dawley rats that were selectively-bred for differences in novelty exploration. Selective breeding for low vs. high locomotor response to novelty produced rat lines that differ in behavioral domains relevant to anxiety and depression, particularly the RDoC Negative Valence domains, including acute threat, potential threat, and loss. Bred Low Novelty Responder (LR) rats, relative to their High Responder (HR) counterparts, display high levels of behavioral inhibition, conditioned and unconditioned fear, avoidance, passive stress coping, anhedonia, and psychomotor retardation. The HR/LR traits are heritable, emerge in the first weeks of life, and appear to be driven by alterations in the developing amygdala and hippocampus. Epigenomic and transcriptomic profiling in the developing and adult HR/LR brain suggest that DNA methylation and microRNAs, as well as differences in monoaminergic transmission (dopamine and serotonin in particular), contribute to their distinct behavioral phenotypes. This work exemplifies ways that animal models such as the HR/LR rats can be effectively used to study neural and molecular factors driving emotional behavior, which may pave the way toward improved understanding the neurobiological mechanisms involved in emotional disorders. Selective breeding for low vs. high locomotor response to novelty produced rat lines that differ in behavioral domains relevant to anxiety and depression. Low Novelty Responder rats show high levels of behavioral inhibition, fear, passive stress coping, and anhedonia. Molecular studies identified epigenetic and gene expression changes that contribute to these distinct behavioral phenotypes, which mayaid understanding the biological mechanisms involved in emotional disorders.
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影响因子：
3.1
作者：
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