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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.
International Journal of Molecular Sciences
|March 13, 2025
Summary
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.
