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Sexually dimorphic effects of lipopolysaccharide on spatial memory
Madison B Cloud1, Sophia K Jordan1, Rachel A Kohman1
1University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA.
Physiology & Behavior
|May 2, 2026
Summary
Lipopolysaccharide (LPS) impairs spatial memory in male mice but not females. Sex differences in hippocampal inflammation may explain these distinct cognitive effects, highlighting the need to study both sexes.
Area of Science:
- Neuroscience
- Immunology
- Behavioral Science
Background:
- Lipopolysaccharide (LPS) administration is known to cause memory deficits.
- Previous research on LPS and cognition has largely focused on male subjects.
- Emerging evidence suggests sex-based differences in cognitive responses to LPS.
Purpose of the Study:
- To investigate sex differences in spatial learning and memory following LPS administration.
- To determine if LPS affects spatial memory differently in female and male mice.
- To explore potential mechanisms underlying observed sex differences in cognitive response to LPS.
Main Methods:
- Adult female and male C57BL/6J mice were used.
- Spatial learning and memory assessed using the hidden platform water maze task.
- LPS (0.25 mg/kg) administered before water maze training.
- Hippocampal and splenic inflammatory markers analyzed.
- Hippocampal expression of interleukin type 1 receptor accessory proteins (AcP and AcPb) quantified.
Main Results:
- LPS administration impaired spatial memory in males but not in females.
- Sexes exhibited differential behavioral search strategies during the probe trial.
- LPS induced similar hippocampal and splenic inflammatory marker expression in both sexes.
- Males displayed higher hippocampal expression of AcP and AcPb compared to females.
Conclusions:
- Sex-dependent effects of LPS on spatial memory were observed in the water maze.
- Differential expression of hippocampal interleukin type 1 receptor accessory proteins may contribute to sex differences in LPS-induced cognitive deficits.
- These findings underscore the importance of considering biological sex in studies of LPS-induced neuroinflammation and cognitive function.
