Low molecular weight polysialic acid prevents lipopolysaccharide-induced inflammatory dopaminergic neurodegeneration in humanized SIGLEC11 transgenic mice

Here, we investigated the effect of low molecular weight polysialic acid (polySia avDP20) on inflammatory neurodegeneration. SIGLEC11 transgenic and wild type control (WT) mice were treated intraperitoneally daily over four consecutive days with 1 µg/gbw/day LPS in conjunction with 10 μg/gbw polySia avDP20. Repeated LPS injections led to inflammation and neuronal loss in the brains of WT and SIGLEC11 transgenic mice. Transcriptome analysis by RNA-seq of total brain tissue indicated that treatment with polySia avDP20 prevented the LPS-induced upregulation of genes belonging to inflammation, TLR signaling, phagocytosis, and complement-related pathways in SIGLEC11 transgenic but not wild type mice. Examination of brain mRNA profiles 19 days after repeated LPS or PBS (vehicle control) treatment in conjunction with low molecular weight polysialic acid (polySia avDP20) or PBS (vehicle control) application of 3-months old male WT and SIGLEC11 transgenic mice by RNA-Seq (5-7 animals per group).