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

<p>Abstract</p> <p>Background</p> <p>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 <it>B. burgdorferi</it>-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism.</p> <p>Methods</p> <p>In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of <it>B. burgdorferi</it> (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 <it>t</it> test assuming unequal variances when appropriate.</p> <p>Results</p> <p>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 <it>B. burgdorferi</it> had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward <it>B. burgdorferi</it> and presence of the bacteria in the central nervous system.</p> <p>Conclusions</p> <p>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.</p

Modulation of microglial pro-inflammatory and neurotoxic activity for the treatment of Parkinson’s disease

Parkinson’s disease (PD) is a debilitating movement disorder resulting from a progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. Molecular cloning studies have identified nearly a dozen genes or loci that are associated with small clusters of mostly early onset and genetic forms of PD. The etiology of the vast majority of PD cases remains unknown, and the precise molecular and biochemical processes governing the selective and progressive degeneration of the nigrostriatal dopaminergic pathway are poorly understood. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Studies of postmortem PD brains and various cellular and animal models of PD in the last 2 decades strongly suggest that the generation of proinflammatory and neurotoxic factors by the resident brain immune cells, microglia, plays a prominent role in mediating the progressive neurodegenerative process. This review discusses literature supporting the possibility of modulating the activity of microglia as a neuroprotective strategy for the treatment of PD