罗伊氏乳杆菌对新生小鼠母婴分离应激的影响。
Lactobacillus reuteri effects on maternal separation stress in newborn mice.
机构信息
Departments of Pediatrics at McGovern Medical School, the University of Texas Health Science Center at Houston, Houston, TX, USA.
Departments of Neurology at McGovern Medical School, the University of Texas Health Science Center at Houston, Houston, TX, USA.
出版信息
Pediatr Res. 2021 Nov;90(5):980-988. doi: 10.1038/s41390-021-01374-0. Epub 2021 Feb 2.
BACKGROUND
Probiotic Lactobacillus reuteri DSM 17938 (LR 17938) is beneficial to infants with colic. To understand its mechanism of action, we assessed ultrasonic vocalizations (USV) and brain pain/stress genes in newborn mice exposed to maternal separation stress.
METHODS
Pups were exposed to unpredictable maternal separation (MSU or SEP) or MSU combined with unpredictable maternal stress (MSU + MSUS or S + S), from postnatal days 5 to 14. USV calls and pain/stress/neuroinflammation-related genes in the brain were analyzed.
RESULTS
We defined 10 different neonatal call patterns, none of which increased after MSU. Stress reduced overall USV calls. Orally feeding LR 17938 also did not change USV calls after MSU. However, LR 17938 markedly increased vocalizations in mice allowed to stay with their dams. Even though LR 17938 did not change MSU-related calls, LR 17938 modulated brain genes related to stress and pain. Up-regulated genes following LR 17938 treatment were opioid peptides, kappa-opioid receptor 1 genes, and CD200, important in anti-inflammatory signaling. LR 17938 down-regulated CCR2 transcripts, a chemokine receptor, in the stressed neonatal brain.
CONCLUSIONS
USV calls in newborn mice are interpreted as "physiological calls" instead of "cries." Feeding LR 17938 after MSU did not change USV calls but modulated cerebral genes favoring pain and stress reduction and anti-inflammatory signaling.
IMPACT
We defined mouse ultrasonic vocalization (USV) call patterns in this study, which will be important in guiding future studies in other mouse strains. Newborn mice with maternal separation stress have reduced USVs, compared to newborn mice without stress, indicating USV calls may represent "physiological calling" instead of "crying." Oral feeding of probiotic Lactobacillus reuteri DSM 17938 raised the number of calls when newborn mice continued to suckle on their dams, but not when mice were under stress. The probiotic bacteria had a dampening effect on monocyte activation and on epinephrine and glutamate-related stress gene expression in the mouse brain.
背景
益生菌罗伊氏乳杆菌 DSM 17938（LR 17938）对患有绞痛的婴儿有益。为了了解其作用机制，我们评估了暴露于母体分离应激的新生小鼠的超声发声（USV）和大脑疼痛/应激/神经炎症基因。
方法
从出生后第 5 天到第 14 天，将幼崽暴露于不可预测的母体分离（MSU 或 SEP）或 MSU 与不可预测的母体应激（MSU+MSUS 或 S+S）。分析大脑中的 USV 叫声和与疼痛/应激/神经炎症相关的基因。
结果
我们定义了 10 种不同的新生叫声模式，其中没有一种在 MSU 后增加。应激减少了整体 USV 叫声。口服给予 LR 17938 后，MSU 后 USV 叫声也没有变化。然而，LR 17938 显著增加了与母鼠一起饲养的小鼠的发声。即使 LR 17938 没有改变与 MSU 相关的叫声，LR 17938 也调节了与应激和疼痛相关的大脑基因。LR 17938 处理后上调的基因包括阿片肽、κ-阿片受体 1 基因和 CD200，这在抗炎信号中很重要。LR 17938 下调了应激新生大脑中的趋化因子受体 CCR2 转录物。
结论
新生小鼠的 USV 叫声被解释为“生理叫声”而不是“哭声”。MSU 后给予 LR 17938 喂养不会改变 USV 叫声，但会调节大脑基因，有利于减轻疼痛和应激以及抗炎信号。
影响
我们在这项研究中定义了小鼠超声发声（USV）叫声模式，这将对指导其他小鼠品系的未来研究很重要。与没有应激的新生小鼠相比，有母体分离应激的新生小鼠的 USV 叫声减少，表明 USV 叫声可能代表“生理叫声”而不是“哭声”。当新生小鼠继续吸吮母鼠时，口服给予益生菌罗伊氏乳杆菌 DSM 17938 会增加叫声次数，但当小鼠处于应激状态时则不会。这种益生菌对小鼠大脑中单核细胞激活以及去甲肾上腺素和谷氨酸相关应激基因表达有抑制作用。
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