Alpha-tocopherol attenuates NFkappaB activation and pro-inflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior.

  • Godbout J
  • Berg B
  • Krzyszton C
 et al. 
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Abstract

This study was conducted to determine if alpha-tocopherol facilitates recovery from lipopolysaccharide (LPS)-induced sickness behavior through a NFkappaB-dependent mechanism. In the first study, 3 daily intraperitoneal (i.p.) injections of alpha-tocopherol (20 mg) improved recovery from sickness behavior induced by i.p. injected LPS. Furthermore, alpha-tocopherol pretreatment attenuated LPS-activated NFkappaB and pro-inflammatory cytokine production in brain. In addition, inhibiting NFkappaB activity in the brain specifically by ICV injection of a NFkappaB decoy prior to LPS, significantly accelerated recovery from LPS-induced sickness behavior. Taken together, these data indicate alpha-tocopherol modulates sickness behavior and inflammatory cytokine production in the brain through an NFkappaB-dependent pathway.

Author-supplied keywords

  • Analysis of Variance
  • Animals
  • Antioxidants
  • Antioxidants: pharmacology
  • Antioxidants: therapeutic use
  • Behavior, Animal
  • Behavioral Symptoms
  • Behavioral Symptoms: chemically induced
  • Behavioral Symptoms: drug therapy
  • Brain
  • Brain Chemistry
  • Brain Chemistry: drug effects
  • Brain: drug effects
  • Brain: metabolism
  • Chromatography, High Pressure Liquid
  • Chromatography, High Pressure Liquid: methods
  • Cytokines
  • Cytokines: metabolism
  • Drug Interactions
  • Electrophoretic Mobility Shift Assay
  • Electrophoretic Mobility Shift Assay: methods
  • Enzyme Activation
  • Enzyme Activation: drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunosorbent Assay: methods
  • Exploratory Behavior
  • Exploratory Behavior: drug effects
  • Injections, Intraventricular
  • Injections, Intraventricular: methods
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protein-Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases: metabolism
  • Recovery of Function
  • Recovery of Function: drug effects
  • alpha-Tocopherol
  • alpha-Tocopherol: pharmacology
  • alpha-Tocopherol: therapeutic use

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Authors

  • J P Godbout

  • B M Berg

  • C Krzyszton

  • R W Johnson

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