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小鼠胃迷走神经传入信号的妊娠相关可塑性

Pregnancy-related plasticity of gastric vagal afferent signals in mice.

作者信息

Li Hui, Clarke Georgia S, Christie Stewart, Ladyman Sharon R, Kentish Stephen J, Young Richard L, Gatford Kathryn L, Page Amanda J

机构信息

Adelaide Medical School, University of Adelaide, Adelaide, Australia.

Nutrition, Diabetes and Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2021 Jan 1;320(2):G183-G192. doi: 10.1152/ajpgi.00357.2020. Epub 2020 Nov 18.

DOI:10.1152/ajpgi.00357.2020
PMID:33206550
Abstract

Gastric vagal afferents (GVAs) sense food-related mechanical stimuli and signal to the central nervous system, to integrate control of meal termination. Pregnancy is characterized by increased maternal food intake, which is essential for normal fetal growth and to maximize progeny survival and health. However, it is unknown whether GVA function is altered during pregnancy to promote food intake. This study aimed to determine the mechanosensitivity of GVAs and food intake during early, mid-, and late stages of pregnancy in mice. Pregnant mice consumed more food compared with nonpregnant mice, notably in the light phase during mid- and late pregnancy. The increased food intake was predominantly due to light-phase increases in meal size across all stages of pregnancy. The sensitivity of GVA tension receptors to gastric distension was significantly attenuated in mid- and late pregnancy, whereas the sensitivity of GVA mucosal receptors to mucosal stroking was unchanged during pregnancy. To determine whether pregnancy-associated hormonal changes drive these adaptations, the effects of estradiol, progesterone, prolactin, and growth hormone on GVA tension receptor mechanosensitivity were determined in nonpregnant female mice. The sensitivity of GVA tension receptors to gastric distension was augmented by estradiol, attenuated by growth hormone, and unaffected by progesterone or prolactin. Together, the data indicate that the sensitivity of GVA tension receptors to tension is reduced during pregnancy, which may attenuate the perception of gastric fullness and explain increased food intake. Further, these adaptations may be driven by increases in maternal circulating growth hormone levels during pregnancy. This study provides first evidence that gastric vagal afferent signaling is attenuated during pregnancy and inversely associated with meal size. Growth hormone attenuated mechanosensitivity of gastric vagal afferents, adding support that increases in maternal growth hormone may mediate adaptations in gastric vagal afferent signaling during pregnancy. These findings have important implications for the peripheral control of food intake during pregnancy.

摘要

胃迷走传入神经(GVAs)感知与食物相关的机械刺激,并向中枢神经系统发送信号,以整合对进餐终止的控制。怀孕的特征是母体食物摄入量增加,这对胎儿的正常生长以及使后代的生存和健康最大化至关重要。然而,尚不清楚怀孕期间GVAs功能是否发生改变以促进食物摄入。本研究旨在确定小鼠怀孕早期、中期和晚期GVAs的机械敏感性和食物摄入量。与未怀孕的小鼠相比,怀孕小鼠摄入的食物更多,尤其是在怀孕中期和晚期的光照阶段。食物摄入量的增加主要是由于怀孕各阶段光照期进餐量的增加。怀孕中期和晚期,GVA张力感受器对胃扩张的敏感性显著减弱,而怀孕期间GVA黏膜感受器对黏膜抚摸的敏感性没有变化。为了确定与怀孕相关的激素变化是否驱动了这些适应性变化,在未怀孕的雌性小鼠中测定了雌二醇、孕酮、催乳素和生长激素对GVA张力感受器机械敏感性的影响。雌二醇增强了GVA张力感受器对胃扩张的敏感性,生长激素使其减弱,而孕酮或催乳素则无影响。总之,数据表明怀孕期间GVA张力感受器对张力的敏感性降低,这可能会减弱对胃饱腹感的感知并解释食物摄入量的增加。此外,这些适应性变化可能是由怀孕期间母体循环生长激素水平的升高所驱动的。本研究提供了首个证据,表明怀孕期间胃迷走传入信号减弱,且与进餐量呈负相关。生长激素减弱了胃迷走传入神经的机械敏感性,进一步支持了母体生长激素的增加可能介导怀孕期间胃迷走传入信号适应性变化的观点。这些发现对怀孕期间食物摄入的外周控制具有重要意义。

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