![]() On the other hand, inhibition of Syk reduced microglial phagocytosis of beads, synapses and neurons. Syk inhibition also had no effect on the morphological transition of microglia exposed to LPS. However, in the presence of LPS, Syk inhibition had relatively little effect on microglial density (reduced by 0–30%) and opposing effects on the release of two pro-inflammatory cytokines (IL-6 decreased by about 45%, TNFα increased by 80%). In the absence of LPS, Syk inhibition depleted microglia from the cultures and induced some microglial death. Syk inhibition also prevented the spontaneous loss of neurons from older neuron-glia cultures. ![]() We found that the Syk inhibitors BAY61-3606 and P505-15 (at 1 and 10 μM, respectively) completely prevented the neuronal loss induced by LPS, which was microglia-dependent. Here, we have tested whether Syk inhibitors can prevent microglia-dependent neurodegeneration induced by lipopolysaccharide (LPS) in primary neuron-glia cultures. Microglial inflammation and phagocytosis are thought to be regulated by spleen tyrosine kinase (Syk), which is activated by multiple microglial receptors, including TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), implicated in neurodegeneration. Microglia are brain macrophages and play beneficial and/or detrimental roles in many brain pathologies because of their inflammatory and phagocytic activity. Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
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