Early-life infection leads to altered BDNF and IL-1beta mRNA expression in rat hippocampus following learning in adulthood

Brain Behav Immun. 2008 May;22(4):451-5. doi: 10.1016/j.bbi.2007.10.003. Epub 2007 Nov 7.

Abstract

Neonatal bacterial infection in rats leads to profound hippocampal-dependent memory impairments following a peripheral immune challenge in adulthood. Here, we determined whether neonatal infection plus an immune challenge in adult rats is associated with impaired induction of brain-derived neurotrophic factor (BDNF) within the hippocampus (CA1, CA3, and dentate gyrus) following fear conditioning. BDNF is well characterized for its critical role in learning and memory. Rats injected on postnatal day 4 with PBS (vehicle) or Escherichia coli received as adults either no conditioning or a single 2min trial of fear conditioning. Half of the rats in the conditioned group then received a peripheral injection of 25mug/kg lipopolysaccharide (LPS) and all were sacrificed 1 or 4h later. Basal (unconditioned) BDNF mRNA did not differ between groups. However, following conditioning, neonatal infection with E. coli led to decreased BDNF mRNA induction in all regions compared to PBS-treated rats. This decrease in E. coli-treated rats was accompanied by a large increase in IL-1beta mRNA in CA1. Taken together, these data indicate that early infection strongly influences the induction of IL-1beta and BDNF within distinct regions of the hippocampus, which likely contribute to observed memory impairments in adulthood.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / genetics*
  • Conditioning, Psychological / physiology*
  • Endotoxemia / immunology
  • Endotoxemia / physiopathology
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / physiopathology*
  • Fear / physiology
  • Female
  • Gene Expression Regulation / immunology
  • Hippocampus / immunology*
  • Interleukin-1beta / genetics*
  • Lipopolysaccharides / pharmacology
  • Male
  • Memory Disorders / immunology
  • Memory Disorders / physiopathology
  • RNA, Messenger / immunology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Brain-Derived Neurotrophic Factor
  • Interleukin-1beta
  • Lipopolysaccharides
  • RNA, Messenger