Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice.

Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice.
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DOI:
10.1002/dev.22289
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发表时间:
2022-09
影响因子:
2.2
通讯作者:
--
中科院分区:
心理学4区
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--
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母体抗生素 (ABx) 暴露会显着扰乱微生物群从母亲到后代的转移,导致与自闭症谱系障碍 (ASD) 等神经发育障碍潜在相关的生态失调。对啮齿动物模型的研究发现,经过 ABx 处理的母鼠对后代的神经行为有长期影响,但断奶前早期的自闭症谱系障碍 (ASD) 相关行为迄今一直被忽视。在这里,我们从妊娠第 12 天到后代出生后第 14 天,将 C57BL/6J 小鼠暴露于溶解在饮用水中的 ABx(5 mg/ml 新霉素、1.25 μg/ml pimaricin、0.075% v/v 乙酸)。寒冷挑战和嗅觉引导的回家方向。此外,我们在行为测试期间和之后获得了幼犬体温调节能力的测量结果。我们发现经过 ABx 处理的母鼠的后代存在许多行为差异(例如,通过幼崽体重、挤作一团时的活动来调节 USV),并提供证据表明其中一些行为影响可能与体温调节缺陷有关,尤其是在较年轻的年龄。我们的结果表明,ABx 不仅会破坏微生物组、体温调节和行为,而且代谢效应可能会混淆对早期接触 ABx 后观察到的行为差异的解释。
Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Studies in rodent models have found long-term neurobehavioral effects in offspring of ABx-treated dams, but ASD-relevant behavior during the early pre-weaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, 0.075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD-relevant behaviors were assayed in offspring, including ultrasonic vocalization production during maternal separation, group huddling in response to cold-challenge, and olfactory-guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx-treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early-life ABx exposure.
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