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脂多糖对怀孕小鼠及其后代焦虑的反向影响。

Inverse effects of lipopolysaccharides on anxiety in pregnant mice and their offspring.

作者信息

Solati Jalal, Kleehaupt Eva, Kratz Oliver, Moll Gunther H, Golub Yulia

机构信息

Department of Child and Adolescent Mental Health, University of Erlangen-Nürnberg, Erlangen, Germany; Department of Biology, College of Science, Karaj branch, Islamic Azad University, Alborz, Iran.

Department of Child and Adolescent Mental Health, University of Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Physiol Behav. 2015 Feb;139:369-74. doi: 10.1016/j.physbeh.2014.10.016. Epub 2014 Nov 11.

DOI:10.1016/j.physbeh.2014.10.016
PMID:25447752
Abstract

This study aimed to evaluate the effects of the bacterial lipopolysaccharide (LPS) exposure during early pregnancy on anxiety-related behaviour of both pregnant female mice and their male offspring. Pregnant NMRI mice were treated with subcutaneous injections of LPS (30, 60, 120, 240 and 480 μg/kg) on the tenth gestational day of pregnancy. Pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and corticosterone levels, were measured in maternal serum 1.5h following the LPS injections. Baseline anxiety levels of pregnant mice (1.5h after LPS administration) and their male offspring (at postnatal days 60-70) were investigated with the elevated plus maze (EPM) test. In addition, anxiety levels in the offspring were measured after 2h restraint stress or TNF-α (10 μg/kg) administration. Our results demonstrate that LPS administration induces anxiety-like behaviour and a significant increase in cytokines and corticosterone levels in maternal serum. However, in male offspring, prenatal LPS administration has no significant effects on serum cytokines and corticosterone secretion with an exception of the lowest LPS dose that slightly reduced corticosterone levels. Interestingly, prenatal LPS treatment seemed to decrease the baseline anxiety levels, while pretreatment with restraint stress or TNF-α abolished this anxiolytic effects. In summary, our results suggest that prenatal exposure to LPS during early pregnancy may result in reduced baseline anxiety in adult male offspring.

摘要

本研究旨在评估妊娠早期暴露于细菌脂多糖(LPS)对妊娠雌性小鼠及其雄性后代焦虑相关行为的影响。妊娠第10天,对妊娠的NMRI小鼠皮下注射LPS(30、60、120、240和480μg/kg)。在注射LPS后1.5小时,检测母体血清中促炎细胞因子,如TNF-α、IL-1β、IL-6和皮质酮水平。采用高架十字迷宫(EPM)试验,研究妊娠小鼠(LPS给药后1.5小时)及其雄性后代(出生后60-70天)的基线焦虑水平。此外,在对后代进行2小时束缚应激或给予TNF-α(10μg/kg)后,测量其焦虑水平。我们的结果表明,给予LPS会诱导母体血清中出现焦虑样行为,并使细胞因子和皮质酮水平显著升高。然而,在雄性后代中,产前给予LPS对血清细胞因子和皮质酮分泌没有显著影响,但最低剂量的LPS会轻微降低皮质酮水平。有趣的是,产前LPS治疗似乎会降低基线焦虑水平,而束缚应激或TNF-α预处理则会消除这种抗焦虑作用。总之,我们的结果表明,妊娠早期产前暴露于LPS可能会导致成年雄性后代的基线焦虑降低。

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