Deficits in cognitive function are associated with neuroinflammatory changes, typified by activation of glial cells and an alteration of the pro-and anti-inflammatory cytokine balance in the brain. Although there is evidence to suggest that activation of microglia is regulated by interaction with other cell types in the brain, the mechanism(s) involved is poorly understood. Here, we provide evidence that interaction between CD200 and its receptor plays a role in modulating microglial activation under conditions of chronic and acute inflammation of the brain. We report that interleukin-4 (IL-4) plays a central role in modulating expression of CD200 and identify a mechanism by which IL-4 directly controls microglial cell activation. Our findings provide the first demonstration of a role for IL-4 in modulating CD200 expression and suggest a mechanism for regulation of microglial activation in the intact CNS under inflammatory conditions.
Administration of VP025 (Vasogen Inc.), a novel drug formulation based on phospholipid nanoparticles incorporating phosphatidylglycerol, has previously been shown to have a neuroprotective effect in the brain. We examined the effect of VP025 in a rat model of Parkinson's disease, the 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle. VP025 or phosphate-buffered saline (PBS) was administered to rats 14 days, 13 days and 1 day before the unilateral 6-OHDA lesion. Functional integrity of nigrostriatal dopaminergic neurons was assessed 7 and 21 days later by amphetamine-induced rotational testing and we observed that rotational counts were significantly less in rats that were pretreated with VP025 compared with PBS-pretreated 6-OHDA-lesioned rats. Neurochemical analysis at 10 and 28 days after lesion revealed that VP025 protected against a 6-OHDA-induced decrease in concentrations of striatal dopamine and its metabolites. Immunocytochemical studies of the ipsilateral substantia nigra showed that VP025 significantly inhibited 6-OHDA-induced loss of dopaminergic neurons. We also observed that increases in immunostaining for activated microglia and for activated p38 in dopaminergic neurons of 6-OHDA-lesioned rats were prevented by VP025. This study shows that VP025 has significant protective effects on the 6-OHDA-lesioned nigrostriatal pathway and may therefore have potential for the treatment of Parkinson's disease.
Kefir is a fermented milk beverage consumed for nutritional and health tonic benefits in many parts of the world. It is produced by the fermentation of milk with a consortium of bacteria and yeast embedded within a polysaccharide matrix. This consortium is not well defined and can vary substantially between kefir grains. There are little data on the microbial stability of kefir grains, nor on interactions between microbes in the grain and in the milk. To study this, a grain was split, with one half of each stored at -20°C and the other half passaged repeatedly in whole unpasteurised milk. Grains passaged in the unpasteurised milk recovered vigour and acquired the yeast Kluyveromyces marxainus from the milk which was confirmed to be the same strain by molecular typing. Furthermore, these passaged grains produced kefir that was distinguished chemically and organoleptically from the stored grains. Some changes in ultrastructure were also observed by scanning electron microscopy. The study showed that kefir grains can acquire yeast from their environment and the final product can be influenced by these newly acquired yeasts. Kluyveromyces marxianus is considered to be responsible for some of the most important characteristics of kefir so the finding that this yeast is part of the less stable microbiota is significant.
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