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Hyperammonemia increases sensitivity to LPS.

Juan C Marini1, Suzanne R Broussard

  • 1Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Molecular Genetics and Metabolism
|February 25, 2006
PubMed
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Chronic hyperammonemia impairs cognition and increases sensitivity to lipopolysaccharide (LPS). This condition exacerbates sickness behaviors and learning deficits in mice, highlighting a link between ammonia levels and immune response.

Area of Science:

  • Neuroscience
  • Immunology
  • Metabolic Disorders

Background:

  • Hyperammonemia is associated with metabolic and cognitive dysfunction.
  • The impact of chronic hyperammonemia on immune system sensitivity, particularly to lipopolysaccharide (LPS), is not fully understood.

Purpose of the Study:

  • To investigate the effects of chronic hyperammonemia on sickness behavior and cognitive function in mice.
  • To determine if chronic hyperammonemia alters sensitivity to LPS challenge.

Main Methods:

  • Sparse-fur (Otc(spf-ash)) mice with chronic hyperammonemia and wild-type littermates were challenged with LPS or saline.
  • Sickness behavior, motivation, plasma cytokine concentrations, ammonia levels, and cognitive performance (Y-maze, Morris water maze) were assessed.

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Main Results:

  • Otc(spf-ash) mice exhibited more pronounced and prolonged sickness behavior after LPS challenge.
  • LPS significantly increased plasma concentrations of numerous pro-inflammatory cytokines in both genotypes.
  • Hyperammonemic mice showed significantly poorer performance in learning and memory tasks compared to controls.

Conclusions:

  • Chronic hyperammonemia impairs cognitive functions, including learning and memory.
  • Hyperammonemia induces a state of hypersensitivity to LPS, suggesting a link between ammonia toxicity and immune dysregulation.