Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.
There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.
Bilbo
Staci D
SD
Duke University, Department of Psychology & Neuroscience, Durham, NC 27708, USA. staci.bilbo@duke.edu <staci.bilbo@duke.edu>
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology*; D003214:Conditioning, Classical; D004927:Escherichia coli Infections; D005239:Fear / Q000502:physiology; D007239:Infections; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism*; D009483:Neuropsychological Tests; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate
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