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

https://doi.org/10.1016/j.bbi.2007.10.003Get rights and content

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 2 min trial of fear conditioning. Half of the rats in the conditioned group then received a peripheral injection of 25 μg/kg lipopolysaccharide (LPS) and all were sacrificed 1 or 4 h 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-1β mRNA in CA1. Taken together, these data indicate that early infection strongly influences the induction of IL-1β and BDNF within distinct regions of the hippocampus, which likely contribute to observed memory impairments in adulthood.

Introduction

BDNF is well characterized for its role in learning and memory. Its expression is critical for the induction and maintenance of events involved in synaptic plasticity (Korte et al., 1995, Messaoudi et al., 2002) as well as neurogenesis and neuroprotection (Lee et al., 2002). BDNF mRNA is rapidly induced within the hippocampus following contextual fear conditioning (Hall et al., 2000), a hippocampal-dependent memory task, and BDNF is necessary for at least 4 h after training for long-term memory consolidation (Alonso et al., 2002). We have demonstrated that rats infected with bacteria as neonates exhibit profound long-term memory impairments in adulthood, but only if a peripheral immune challenge (lipopolysaccharide; LPS) is given around the time of learning (Bilbo et al., 2005a, Bilbo et al., 2005b, Bilbo et al., 2006). Adult rats infected as neonates also exhibit exaggerated brain interleukin (IL)-1β responses to the LPS compared to controls (Bilbo et al., 2005a), a cytokine which impairs BDNF induction (Barrientos et al., 2004) and signal transduction (Tong et al., 2007), as well as memory (Barrientos et al., 2002). Thus, the goal of this experiment was to determine whether neonatal infection in rats is associated with (1) impaired induction of BDNF and (2) exaggerated IL-1β within the hippocampus following fear conditioning.

Section snippets

Animals

Adult male and female Sprague–Dawley rats (70 days) were obtained from Harlan (Indianapolis, IN) and housed in same sex pairs in polypropylene cages with ad libitum access to food and water. The colony was maintained at 22 °C on a 12:12-h light:dark cycle (lights on at 0600 MST). Following acclimation to experimental conditions, males and females were paired into breeders. Sentinel animals were housed in the colony room and screened periodically for the presence of common rodent diseases; all

Results and discussion

Basal (unconditioned) BDNF mRNA did not differ by neonatal treatment in any region. In dorsal CA1, a significant group effect revealed that neonatal infection significantly decreased the induction of BDNF following conditioning overall compared to PBS rats (F1,45 = 17.2, p < 0.001; Fig. 1). A significant injection × time interaction revealed that expression was lowest in both 4 h LPS groups (F1,45 = 5.3, p = 0.02). Although the three-way interaction was not significant, it is striking that BDNF

Acknowledgments

The authors thank Matt Frank for expertise with PCR. Supported in part by NIH Grant MH076320-02.

References (23)

  • M. Alonso et al.

    BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation

    Hippocampus

    (2002)
  • Cited by (93)

    • Sex differences in microglia as a risk factor for Alzheimer’s disease

      2021, Sex and Gender Differences in Alzheimer’s Disease
    View all citing articles on Scopus
    View full text