Short CommunicationEarly-life infection leads to altered BDNF and IL-1β mRNA expression in rat hippocampus following learning 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)
- et al.
Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus
Behav. Brain Res.
(2002) - et al.
BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration
J. Neuroimmunol.
(2004) - et al.
Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood
Brain Behav. Immun.
(2007) - et al.
A behavioural characterization of neonatal infection-facilitated memory impairment in adult rats
Behav. Brain Res.
(2006) - et al.
Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction
Anal. Biochem.
(1987) - et al.
Spatial learning impairment in mice infected with Legionella pneumophila or administered exogenous interleukin-1-beta
Brain Behav. Immun.
(1995) - et al.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method
Methods
(2001) - et al.
Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase
Neurobiol. Aging
(2004) - et al.
IL-1beta regulation of BDNF expression in rat cultured hypothalamic neurons depends on the presence of glial cells
Neurochem. Int.
(2006) - et al.
Physiology of BDNF: focus on hypothalamic function
Front. Neuroendocrinol.
(2004)
BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation
Hippocampus
Cited by (93)
Post-operative cognitive dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary DHA supplementation
2024, Brain, Behavior, and ImmunityCD8<sup>+</sup> T cells contribute to diet-induced memory deficits in aged male rats
2023, Brain, Behavior, and ImmunityDietary DHA prevents cognitive impairment and inflammatory gene expression in aged male rats fed a diet enriched with refined carbohydrates
2021, Brain, Behavior, and ImmunitySex differences in microglia as a risk factor for Alzheimer’s disease
2021, Sex and Gender Differences in Alzheimer’s Disease