Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis

Abstract

BackgroundWe 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.MethodsIn 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.ResultsWe 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.ConclusionsThese 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.

Acetate Supplementation as a Means of Inducing Glioblastoma Stem-Like Cell Growth Arrest

“…GTA likely contributes to the acetylation of a plethora of proteins since it is primarily viewed as a delivery vehicle for acetate (Mathew et al, ; Madhavarao et al, ; Arun et al, ,; Reisenauer et al, ; Soliman and Rosenberger, ; Brissette et al, ; Soliman et al, ; Bhatt et al, ). The identification of 3,600 acetylation sites on 1,750 proteins indicates that the prevalence of acetylation rivals that of phosphorylation as a post‐translational modification (Choudhary et al, ).…”

Acetate Reduces PGE2 Release and Modulates Phospholipase and Cyclooxygenase Levels in Neuroglia Stimulated with Lipopolysaccharide

“…These data suggest that acetate treatment can disrupt eicosanoid signaling in astrocytes, and alters the levels of enzymes involved in eicosanoid release in microglia. The neuroglial cell type-distinct effects of acetate on eicosanoid signaling, and possible chromatin remodeling, may contribute to the distinct anti-inflammatory response found with acetate supplementation both in vivo [3, 4] and in vitro [8, 9]. …”

“…Acetate supplementation reduces tremor phenotype in a rat model of Canavan disease [1], reduces injury in an experimental model of head trauma [2], and reduces neuroglia activation in rat models of neuroinflammation [3] and Lyme neuroborreliosis [4]. Acetate supplementation further increases brain acetyl-CoA levels [3], mitochondrial acetyl-CoA metabolism [5], and alters brain histone acetylation in a time- and site-specific pattern in normal animals [6] and in rats subjected to neuroinflammation [7].…”

Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

“…Increasing neuronal PCr stores protects neurons from hypoxic damage, glutamate toxicity, and Aβ-induced toxicity (Balestrino et al, 2002; Balestrino et al, 1999; Brewer and Wallimann, 2000) and is also neuroprotective in animal models of Huntington’s disease (Matthews et al, 1998), Parkinson’s disease (Matthews et al, 1999), and amyotrophic lateral sclerosis (Klivenyi et al, 1999). Interestingly, acetate supplementation prevents ATP loss, and attenuates neuroglia activation in rat models of traumatic brain injury (Arun et al, 2010), neuroinflammation (Reisenauer et al, 2011), and Lyme neuroborreliosis (Brissette et al, 2012). In brain, acetate is preferentially utilized by astrocytes (Waniewski and Martin, 1998) and is considered as a glial-specific substrate since labeled acetate is mainly incorporated into the synthetic astrocytic-glutamine pool (Minchin and Beart, 1975).…”