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Articles, Behavioral/Systems/Cognitive

Microglia and Memory: Modulation by Early-Life Infection

Lauren L. Williamson, Paige W. Sholar, Rishi S. Mistry, Susan H. Smith and Staci D. Bilbo
Journal of Neuroscience 26 October 2011, 31 (43) 15511-15521; DOI: https://doi.org/10.1523/JNEUROSCI.3688-11.2011
Lauren L. Williamson
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Paige W. Sholar
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Rishi S. Mistry
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Susan H. Smith
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Staci D. Bilbo
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Abstract

The proinflammatory cytokine interleukin-1β (IL-1β) is critical for normal hippocampus (HP)-dependent cognition, whereas high levels can disrupt memory and are implicated in neurodegeneration. However, the cellular source of IL-1β during learning has not been shown, and little is known about the risk factors leading to cytokine dysregulation within the HP. We have reported that neonatal bacterial infection in rats leads to marked HP-dependent memory deficits in adulthood. However, deficits are only observed if unmasked by a subsequent immune challenge [lipopolysaccharide (LPS)] around the time of learning. These data implicate a long-term change within the immune system that, upon activation with the “second hit,” LPS, acutely impacts the neural processes underlying memory. Indeed, inhibiting brain IL-1β before the LPS challenge prevents memory impairment in neonatally infected (NI) rats. We aimed to determine the cellular source of IL-1β during normal learning and thereby lend insight into the mechanism by which this cytokine is enduringly altered by early-life infection. We show for the first time that CD11b+ enriched cells are the source of IL-1β during normal HP-dependent learning. CD11b+ cells from NI rats are functionally sensitized within the adult HP and produce exaggerated IL-1β ex vivo compared with controls. However, an exaggerated IL-1β response in vivo requires LPS before learning. Moreover, preventing microglial activation during learning prevents memory impairment in NI rats, even following an LPS challenge. Thus, early-life events can significantly modulate normal learning-dependent cytokine activity within the HP, via a specific, enduring impact on brain microglial function.

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The Journal of Neuroscience: 31 (43)
Journal of Neuroscience
Vol. 31, Issue 43
26 Oct 2011
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Microglia and Memory: Modulation by Early-Life Infection
Lauren L. Williamson, Paige W. Sholar, Rishi S. Mistry, Susan H. Smith, Staci D. Bilbo
Journal of Neuroscience 26 October 2011, 31 (43) 15511-15521; DOI: 10.1523/JNEUROSCI.3688-11.2011

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Microglia and Memory: Modulation by Early-Life Infection
Lauren L. Williamson, Paige W. Sholar, Rishi S. Mistry, Susan H. Smith, Staci D. Bilbo
Journal of Neuroscience 26 October 2011, 31 (43) 15511-15521; DOI: 10.1523/JNEUROSCI.3688-11.2011
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