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Updated: Feb 26, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile
Brittany F Osborne1, Jasmine I Caulfield1, Samantha A Solomotis1
1Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware, 19716.
Insights
Early-life immune activation in rats did not impair juvenile learning but altered brain cytokine expression and reduced white blood cell counts. These effects highlight the lasting impact of neonatal infection on developing immune and neural systems.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Early-life immune activation can have long-term consequences on brain development and function.
- The emergence of hippocampal-dependent learning at P24 presents a critical window to study these effects.
- Lipopolysaccharide (LPS) is a common tool to model immune challenges.
Purpose of the Study:
- To investigate the impact of neonatal immune activation and a subsequent juvenile LPS challenge on learning, brain cytokine expression, and peripheral immunity in juvenile rats.
- To determine if early-life immune insults lead to learning deficits at the onset of hippocampal function.
- To examine sex differences in the response to immune challenges during development.
Main Methods:
- Rats were subjected to neonatal immune activation and later challenged with LPS at P24.
- Hippocampal-dependent learning was assessed using the context pre-exposure facilitation effect paradigm.
- Proinflammatory cytokine expression (IL-1β, IL-6) in the hippocampus and medial prefrontal cortex was measured.
- Peripheral immune function was evaluated by assessing white blood cell counts.
Main Results:
- Neonatal infection did not cause learning deficits in the P24 rats.
- Neonatal infection increased baseline IL-1β in the hippocampus and medial prefrontal cortex.
- Exaggerated IL-1β responses to LPS were observed in the hippocampus, and in females' medial prefrontal cortex.
- IL-6 production was attenuated, and white blood cell counts were reduced following LPS challenge.
Conclusions:
- Neonatal immune activation has detectable effects on the developing brain and immune system in juvenile rats, even without learning deficits.
- Age and ongoing neurodevelopmental processes are crucial factors in understanding cognitive and behavioral outcomes of early-life immune activation.
- Sex differences exist in the neuroinflammatory response to immune challenges during juvenile development.
Abstract:
The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017.
