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

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

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.

Keywords: Anxiety; Corticosterone; Cytokines; Lipopolysaccharides; Mice.

MeSH terms

  • Animals
  • Anxiety / physiopathology*
  • Corticosterone / blood
  • Female
  • Interleukin-1 / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides / toxicity*
  • Male
  • Maternal Behavior / physiology*
  • Maternal Behavior / psychology
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Psychotropic Drugs / administration & dosage
  • Random Allocation
  • Restraint, Physical
  • Stress, Psychological / physiopathology
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Psychotropic Drugs
  • Tumor Necrosis Factor-alpha
  • Corticosterone