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Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose
Yulim Lee1,2,3, Xianshu Ju1,4,5, Jianchen Cui1,2,3,6
1Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
Heliyon
|April 10, 2024
Summary
Low-dose lipopolysaccharide (LPS) causes mitochondrial dysfunction and cognitive decline in aged mice, preceding neuroinflammation. This highlights mitochondria as a therapeutic target for delirium in elderly patients.
Area of Science:
- Neuroscience
- Gerontology
- Mitochondrial Biology
Background:
- Delirium, an acute cognitive impairment, often follows inflammatory events in the elderly.
- Mitochondria are implicated in neuroinflammation and cognitive deficits post-LPS, but their role in aged brains under low-grade inflammation is less understood.
Purpose of the Study:
- To investigate the significance of mitochondrial dysfunction in the aged brain following a clinically relevant, low-grade systemic inflammatory stimulus.
- To determine if mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly mice.
Main Methods:
- Old-aged mice (18-20 months) were injected with low-dose lipopolysaccharide (LPS).
- Mitochondrial respiration in the hippocampus was measured 24 hours post-injection.
- Gene expression of IL-1β and cognitive function (Barnes maze, fear chamber) were assessed 48 hours post-injection.
Main Results:
- LPS injection reduced hippocampal mitochondrial respiration (decreased RCR).
- Pro-inflammatory cytokine IL-1β gene expression increased 48 hours post-LPS.
- Cognitive impairments were observed in the Barnes maze and fear chamber tests.
- Young mice showed no significant effects from low-dose LPS.
Conclusions:
- Mitochondrial dysfunction occurs early after low-grade systemic inflammation in aged mice.
- This dysfunction precedes observable neuroinflammation and cognitive decline.
- Mitochondria represent a potential therapeutic target for preventing or treating delirium in the elderly.

