Poster abstracts

Poster number 76 submitted by Jacqueline Lieblein

Mice injected with E.coli as neonates have hyperactive behavior and an increased microglial inflammatory profile

Jacqueline C. Lieblein (Department of Neuroscience, The Ohio State University; Abbott Nutrition), Daniel T. Shea (Institute for Behavioral Medicine Research, The Ohio State University), Yan Huang (Institute for Behavioral Medicine Research, The Ohio State University), Michael T. Bailey (Department of Oral Biology, The Ohio State University), Staci D. Bilbo (Department of Psychology and Neuroscience, The Ohio State University), Jonathan P. Godbout (Department of Neuroscience, The Ohio State University)

Abstract:
Newborns surviving an early-life insult may have greater vulnerability to neuro-developmental complications. We hypothesize that early-life infection (ELI) promotes microglial dysregulation resulting in hyperactivation of these cells following a secondary immune challenge. We have previously published that a hyperactive microglial response corresponds with induction of behavioral complications. Therefore, the purpose of this study was to determine the degree to which an Escherichia coli (E.coli) infection in neonatal BALB/c mice causes locomotor disorders and increases the inflammatory reactivity of microglia. To accomplish this goal, three day old mice were injected subcutaneously with either saline or E.coli. Brain inflammation was confirmed 24 hours after injection by RT-PCR. One and two months after neonatal injection, mice were tested in an open field behavior test for locomotor activity. ELI mice had hyperactive behavior noted by a greater distance traveled and more time moving than early-life PBS control (EPC) mice. To determine the level of inflammatory reactivity in microglia, young adult EPC and ELI mice were peripherally injected with saline or lipopolysaccharide (LPS) to provide a secondary immune challenge. Microglia were isolated 4 or 24 hours after challenge for mRNA analyses. Microglia from adult ELI mice had an amplified inflammatory profile following LPS-challenge compared to EPC mice. Exaggerated inflammatory cytokine production corresponded to increased Iba-1 immunoreactivity of microglia in the amygdala and hippocampus of ELI mice 48 hours following LPS. In conclusion, early-life infection led to hyperactive behavior and elevated microglial reactivity following a secondary immune challenge. Understanding the biochemical and immune complications that result from an early-life insult will provide new therapeutic targets to attenuate neurobehavioral complications, such as attention deficit disorder, autism, and schizophrenia.

References:
Henry CJ, Huang Y, Wynne AM, Godbout JP (2009) Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun 23:309-317.

Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, Sheridan JF, Godbout JP (2008) Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 5:15.

Wynne AM, Henry CJ, Godbout JP (2009) Immune and behavioral consequences of microglial reactivity in the aged brain. Integr Comp Biol 49:254-266.

Keywords: microglia, hyperactivity, neonatal infection