Alpha-tocopherol attenuates NFkappaB activation and pro-inflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior.
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.
Godbout
J P
JP
Division of Nutritional Sciences and Department of Animal Sciences, University of Illinois, 1207 W. Gregory Drive, Urbana, IL 61801, USA.
Berg
B M
BM
Krzyszton
C
C
Johnson
R W
RW
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal; D001526:Behavioral Symptoms / Q000139:chemically induced / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism*; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects; D007276:Injections, Intraventricular / Q000379:methods; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*; D000097782:NF-kappaB-Inducing Kinase
D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D017346:Protein Serine-Threonine Kinases; D024502:alpha-Tocopherol; D000097782:NF-kappaB-Inducing Kinase