title: Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis.
abstract: BACKGROUND
  We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism.
  
  
  METHODS
  In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16). Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by a Tukey's post hoc tests or using a Student's t test assuming unequal variances when appropriate.
  
  
  RESULTS
  We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system.
  
  
  CONCLUSIONS
  These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.
authors.affiliation: Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, North Dakota 58203, USA
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Houdek
authors.forename: Angela M
authors.initials: AM
authors.lastname: Floden
authors.forename: Thad A
authors.initials: TA
authors.lastname: Rosenberger
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D020852:Lyme Neuroborreliosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011938:Rec A Recombinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014280:Triglycerides / Q000008:administration & dosage*
chemical_list: D045784:Abietanes; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D039481:CD11b Antigen; D016207:Cytokines; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; C089760:RecA protein, Acinetobacter calcoaceticus; D014280:Triglycerides; C081556:glyceryl triabietate; D011938:Rec A Recombinases