Nature neurosci—神经科学研究的“实验者效应”:小鼠偏爱女性实验人员,厌恶男性实验人员!!
2023-01-20 神经科学临床和基础 神经科学临床和基础 发表于安徽省
这种人类男性气味诱导的厌恶和应激敏感性是由投射到海马区CA1的内嗅皮质中促肾上腺皮质激素释放因子(CRF)神经元的激活介导的,并且该CRF通路的激活在体内和体外调节氯胺酮的抗抑郁样作用。
中文摘要
科学研究表明,人类实验者的性别会影响小鼠在服用速效抗抑郁剂氯胺酮及其生物活性代谢物(2R,6R)-羟基去甲氯胺酮后的行为和反应。小鼠对男性实验人员的气味表现出厌恶,对女性实验人员的味道表现出偏好,当男性实验人员处理时,小鼠的压力敏感性增加。这种人类男性气味诱导的厌恶和应激敏感性是由投射到海马区CA1的内嗅皮质中促肾上腺皮质激素释放因子(CRF)神经元的激活介导的,并且该CRF通路的激活在体内和体外调节氯胺酮的抗抑郁样作用。这更好地理解了人类实验者性别对啮齿动物研究结果的具体和定量贡献,可以提高研究之间的可复制性,同时也揭示了性别对啮齿动物研究结果存在影响的生物学和药理学机制。
英文摘要
We show that the sex of human experimenters affects mouse behaviors and responses following administration of the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. Mice showed aversion to the scent of male experimenters, preference for the scent of female experimenters and increased stress susceptibility when handled by male experimenters. This human-male-scent-induced aversion and stress susceptibility was mediated by the activation of corticotropin-releasing factor (CRF) neurons in the entorhinal cortex that project to hippocampal area CA1. Exposure to the scent of male experimenters before ketamine administration activated CA1-projecting entorhinal cortex CRF neurons, and activation of this CRF pathway modulated in vivo and in vitro antidepressant-like effects of ketamine. A better understanding of the specific and quantitative contributions of the sex of human experimenters to study outcomes in rodents may improve replicability between studies and, as we have shown, reveal biological and pharmacological mechanisms.
参考文献:Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor. Nat Neurosci. 2022 Sep;25(9):1191-1200. doi: 10.1038/s41593-022-01146-x. Epub 2022 Aug 30.
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