<br>脂磷壁酸是革兰氏阳性菌的细胞壁成分，可诱导睡眠和发烧并抑制进食,Brain, Behavior, and Immunity

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脂磷壁酸是革兰氏阳性菌的细胞壁成分，可诱导睡眠和发烧并抑制进食
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.bbi.2020.12.008
Éva Szentirmai ₁ , Ashley R Massie ₂ , Levente Kapás ₁

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细菌细胞壁的碎片是具有生物活性的微生物分子，对大脑功能具有深远的影响。一些细胞壁成分是革兰氏阳性和革兰氏阴性细菌共有的，例如肽聚糖，而其他细胞壁成分是革兰氏阳性或革兰氏阴性微生物特有的。脂多糖 (LPS) 也称为内毒素，仅存在于革兰氏阴性菌中，而脂磷壁酸 (LTA) 是革兰氏阳性菌特有的。肽聚糖、其片段和脂多糖的作用已得到充分表征，它们会诱导睡眠、发烧和厌食。在本研究中，我们研究了 LTA 对睡眠、体温和食物摄入的调节作用。我们发现，腹腔注射来自枯草芽孢杆菌和金黄色葡萄球菌的 100 和 250 μg LTA 可增加小鼠的非快速眼动睡眠 (NREMS)。这些影响是剂量依赖性的，并且这些变化伴随着运动活动和进食以及发热反应的减少。腹腔注射 10 μg LTA 会引起体温单相升高，而来自枯草芽孢杆菌的 100 和 250 μg LTA 则会引起最初的体温过低，随后出现发热。用 250 μg 金黄色葡萄球菌 LTA 处理可引发单相低温。将来自金黄色葡萄球菌的 300 μg/kg LTA 直接注入门静脉，在大鼠中引起类似的睡眠反应，但不影响体温。 LTA 的睡眠调节作用与小鼠体内的 LPS 相似，但 LTA 的效果似乎较差。这些发现表明，LTA 在宿主体内革兰氏阳性细菌信号传导中的作用类似于 LPS/内毒素在革兰氏阴性微生物信号传导中的作用。 LTA 可能在临床表现的革兰氏阳性细菌感染的疾病反应的发展中发挥作用，并且可能有助于共生肠道微生物群的睡眠信号传导。

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Lipoteichoic acid, a cell wall component of Gram-positive bacteria, induces sleep and fever and suppresses feeding

Fragments of the bacterial cell wall are bioactive microbial molecules that have profound effects on the function of the brain. Some of the cell wall constituents are common to both Gram-positive and Gram-negative bacteria, e.g. peptidoglycans, while other cell wall components are specific to either Gram-positive or Gram-negative microbes. Lipopolysaccharide (LPS), also called endotoxin, is found exclusively in Gram-negative bacteria, while lipoteichoic acid (LTA) is specific to Gram-positive bacteria. The effects of peptidoglycans, their fragments, and LPS are well characterized, they induce sleep, fever and anorexia. In the present study, we investigated the sleep, body temperature and food intake modulating effects of LTA. We found that intraperitoneal injection of 100 and 250 μg LTA from B. subtilis and S. aureus increases non-rapid-eye movement sleep (NREMS) in mice. The effects were dose-dependent, and the changes were accompanied by decreased motor activity and feeding as well as febrile responses. Intraperitoneal injection of 10 μg LTA induced monophasic increases in body temperature, while 100 and 250 μg LTA from B. subtilis induced initial hypothermia followed by fever. Treatment with 250 μg LTA from S. aureus elicited monophasic hypothermia. Administration of 300 μg/kg LTA from S. aureus directly into the portal vein elicited similar sleep responses in rats but did not affect body temperature. The sleep-modulating effects of LTA were similar to that of LPS in mice, although LTA appears to be less potent. These findings suggest that the role of LTA in signaling by Gram-positive bacteria in the host body is analogous to the role of LPS/endotoxin in signaling by Gram-negative microbes. LTA may play a role in the development of sickness response in clinically manifest Gram-positive bacterial infections and may contribute to sleep signaling by the commensal intestinal microbiota.

更新日期：2020-12-01

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