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Age-Related Differences in Lipopolysaccharide-Induced Delirium-like Behavior Implicate the Distinct Microglial
Congli Sun1, Xiaomin Kang2, Xirui Jia2
1Department of Physiology, School of Medicine, Southeast University, Nanjing 210009, China.
Abstract:
As the global population ages, the mechanisms underlying age-related susceptibility to delirium have attracted attention. Given the central role of microglia in the pathogenesis of inflammation-related delirium, we investigated the temporal dynamics of neurobehavioral changes and microglial responses, following lipopolysaccharide (LPS, 200 μg/kg) administration in young and old male C57BL/6 mice. Although a similar illness trajectory across 48 h post-treatment (HPT) was observed in both age groups, old-LPS mice exhibited worsened delirium-like behavior. At 48 HPT, in old but not young mice, significantly decreased hippocampal neuronal activity coincided with microglial overactivation. Widespread hippocampal microglial activation was present at 3 HPT but subsided by 12 HPT in young but not old mice, indicating a generally retarded but prolonged microglial response to LPS challenge in old mice. However, for both age groups, at 3 HPT, p16INK4a-negative microglia (with low abundance in the aged brain) exhibited comparable morphological activation, which was not observed for p16INK4a-positive microglia (highly abundant in the aged brain). These results suggest that age-related susceptibility to LPS-induced delirium-like behavior accompanied by different patterns of microglial response might implicate microglial composition shifts and that optimizing microglial composition represents a promising approach to reduce vulnerability to inflammatory challenge.
Insights
Older mice show heightened susceptibility to inflammation-induced delirium due to prolonged microglial activation and altered brain cell activity. Targeting microglial composition may reduce vulnerability to inflammatory challenges.
Area of Science:
- Neuroscience
- Immunology
- Gerontology
Background:
- Aging populations are increasingly susceptible to delirium.
- Microglia play a key role in inflammation-related delirium.
- Understanding age-related differences in microglial response is crucial.
Purpose of the Study:
- To investigate age-related differences in neurobehavioral and microglial responses to lipopolysaccharide (LPS).
- To explore the temporal dynamics of microglial activation in young versus old mice after LPS challenge.
Main Methods:
- Administration of lipopolysaccharide (LPS) to young and old male C57BL/6 mice.
- Assessment of neurobehavioral changes over 48 hours post-treatment (HPT).
- Analysis of hippocampal neuronal activity and microglial activation patterns at different time points.
Main Results:
- Old mice exhibited worsened delirium-like behavior and decreased hippocampal neuronal activity at 48 HPT.
- Microglial activation was prolonged in old mice compared to young mice.
- p16INK4a-positive microglia, abundant in aged brains, showed less activation compared to p16INK4a-negative microglia.
Conclusions:
- Age-related susceptibility to delirium involves distinct microglial response patterns.
- Shifts in microglial composition may contribute to increased vulnerability to inflammation.
- Modulating microglial composition offers a potential strategy to mitigate inflammatory challenges.
