Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood

Bilbo, Staci D.; Newsum, Nicholas J.; Sprunger, David B.; Watkins, Linda R.; Rudy, Jerry W.; Maier, Steven F.

doi:10.1016/j.bbi.2006.10.005

Cited by 88Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolTryptophan and brain disorders

Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood

Bilbo, Staci D., Newsum, Nicholas J., Sprunger, David B., Watkins, Linda R., Rudy, Jerry W., Maier, Steven F.·2007·Brain Behavior and Immunity

DOI 10.1016/j.bbi.2006.10.005

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Abstract

We have previously demonstrated that bacterial infection (Escherichia coli) in neonatal rats is associated with impaired memory in a fear-conditioning task in adulthood. This impairment, however, is only observed if a peripheral immune challenge (lipopolysaccharide; LPS) is administered around the time of learning. We used a brief separation/handling paradigm to determine if the adult memory impairment associated with neonatal-infection could be prevented. Naturally occurring variations in maternal care promote striking variations in offspring cognitive development, and handling paradigms are used to manipulate the quality and quantity of maternal care. Rats were injected on post natal (P) day 4 with E. coli or PBS, and half from each group were handled for 15 min/day from P4 to 20. All rats were then tested in adulthood. Neonatal handling of rats infected as neonates prevented the increase in microglial cell marker reactivity within the hippocampus, and the exaggerated brain IL-1beta production to LPS normally produced by the infection. Thus, these neural processes were now comparable to levels of non-infected PBS controls. Furthermore, handling completely prevented LPS-induced memory impairment in a context-fear task in adult rats infected as neonates. Finally, neonatal handling dramatically improved spatial learning and memory and decreased anxiety in rats treated early with PBS, but had no beneficial effect on these measures in rats infected as neonates. Taken together, these data suggest that maternal care may profoundly influence neuroinflammatory processes in adulthood, and that infection may also prevent maternal care influences on cognition later in life.

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The memory deficit from neonatal E. coli was only observed if an LPS challenge was administered at the time of learning and could be prevented by daily handling of the neonatal rats, which significantly altered their basal HPA axis activity.
“Intriguingly, the deficit was only observed if an LPS challenge was administered at the time of learning and could be prevented by daily handling of the neonatal rats, which significantly altered their basal HPA axis activity (395).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [395]

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Neonatal Infection Induces Memory Impairments Following an Immune Challenge in Adulthood.
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Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats
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Authors: Bilbo, S. D., Newsum, N. J., Sprunger, D. B., Watkins, L. R., Rudy, J. W., & Maier, S. F.
Affiliations: University of Colorado Boulder (US)
Corresponding author: Bilbo, Staci D.
ORCID: Bilbo, Staci D.
Watkins, Linda R.
Rudy, Jerry W.
Maier, Steven F.
Venue: Brain Behavior and Immunity
Publisher: Elsevier BV
Published: 2007-03
Volume: 21
Issue: 3
Pages: 332-342
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2006.10.005
OpenAlex: W1981275614
Cited by: 88
References: 46
Citations by year: 2024: 1 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 11 · 2014: 8 · 2013: 6 · 2012: 4
FWCI: 1.97
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (MH076320, F32MH076320)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: neonatal handling, maternal care, neonatal infection, Escherichia coli, lipopolysaccharide, neuroinflammation, microglial activation, hippocampus, IL-1β, fear conditioning, spatial learning and memory, anxiety, cognitive development
MeSH terms: Age Factors, Analysis of Variance, Animals, Animals, Newborn, Bacterial Infections, Behavior, Animal, Cognition, Critical Period, Psychological, Fear, Female, Handling, Psychological, Hippocampus, Learning, Lipopolysaccharides, Male, Neuroglia, Stress, Psychological, Neuroimmunomodulation, Interleukin-10, Rats, Sprague-Dawley, Rats

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Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood

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