Neonatal Infection Induces Memory Impairments Following an Immune Challenge in Adulthood.

Abstract

Exposure to infectious agents during early postnatal life often alters glucocorticoid responses to stress and immune outcomes in adulthood. The authors examined whether neonatal infection results in memory impairments in adult animals. Rats infected with Escherichia coli (E. coli) as neonates displayed impaired memory for a recently explored context in adulthood. This impairment, however, was only observed in rats that received a peripheral immune challenge (lipopolysaccharide; LPS) immediately following context exposure. Adult rats treated neonatally with E. coli also had decreased hippocampal astrocytes compared with phosphate-buffered saline-treated rats, but displayed increased astrocyte reactivity in the hippocampus and decreased brain interleukin-1beta following lipopolysaccharide. Infection during development appears to alter glia within the hippocampus, which may contribute to altered cytokine responses and memory impairment.

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

“…In some cases (Bilbo et al, 2005;Shi et al, 2003) a true infection is induced, whereas in other cases, inflammation is induced using LPS (e.g., Boisse et al, 2004;Lante et al, 2007), poly(I:C) (Ellis et al, 2006;Meyer et al, 2006a) or a cytokine (e.g., Samuelsson et al, 2006;Smith et al, 2007). These varied approaches may be important as Schwarz and Bilbo (2011) recently showed that LPS and neonatal (n) E. coli infection in 4 day old rat pups elicit markedly different inflammatory profiles in the brain (similar findings were seen with maternal IL-6 and poly(I:C), in Hsiao and Patterson, 2011).…”

“…There is evidence to suggest that neonatal immune activation alters such responses to LPS administration in adulthood. Bilbo et al (2005) reported that exposure to neonatal (n) E. coli infection on P4 impaired memory for a recently explored context as assessed using a fear conditioning paradigm and produced a rapid increase in hippocampal IL-1β levels in male rats that received an adult LPS challenge on P60 (Bilbo et al, 2005). The authors also showed that the memory impairment seen in the n E. coli rats could be prevented by blocking brain IL-1β synthesis just prior to the context preexposure task (Bilbo et al, 2005).…”

“…Bilbo et al (2005) reported that exposure to neonatal (n) E. coli infection on P4 impaired memory for a recently explored context as assessed using a fear conditioning paradigm and produced a rapid increase in hippocampal IL-1β levels in male rats that received an adult LPS challenge on P60 (Bilbo et al, 2005). The authors also showed that the memory impairment seen in the n E. coli rats could be prevented by blocking brain IL-1β synthesis just prior to the context preexposure task (Bilbo et al, 2005). Similarly the group demonstrated that n E. coli treated male rats showed selective impairments in memory for contextual fear conditioning (hippocampal dependent task) but not memory for auditory-cue fear conditioning (hippocampal independent task) following adult LPS challenge on P90 (Bilbo et al, 2006).…”

“…Cytoarchitectural changes can also be seen in the adult animals exposed to immunogen as neonates such as enlargement of bilateral ventricles and alterations in axonal and dendritic arborization in the parietal cortex and substantia nigra (Fan et al, 2011). Common functional deficits seen in rodent offspring exposed to prenatal or neonatal immune activation include cognitive and social dysfunctions (Bilbo et al, 2005;Bitanihirwe et al, 2010;Ibi et al, 2009;Wang et al, 2010).…”

Alzheimer's Disease (AD)-Like Pathology in Aged Monkeys after Infantile Exposure to Environmental Metal Lead (Pb): Evidence for a Developmental Origin and Environmental Link for AD

“…A study by Bilbo et al (2005) showed that perinatal exposure to an infectious agent affected how the nervous system responded to an immune challenge and memory consolidation later in adulthood. The authors also found that neonatal pathogen exposure decreased the number of adult hippocampal astrocytes, increased their reactivity, and decreased brain IL-1␤ levels after adult lipopolysaccharide exposure.…”